Prediction of quaternary assembly of SARS coronavirus peplomer
Identifieur interne : 000E24 ( Pmc/Corpus ); précédent : 000E23; suivant : 000E25Prediction of quaternary assembly of SARS coronavirus peplomer
Auteurs : Andrea Bernini ; Ottavia Spiga ; Arianna Ciutti ; Stefano Chiellini ; Luisa Bracci ; Xiyun Yan ; Bojian Zheng ; Jiandong Huang ; Ming-Liang He ; Huai-Dong Song ; Pei Hao ; Guoping Zhao ; Neri NiccolaiSource :
- Biochemical and Biophysical Research Communications [ 0006-291X ] ; 2004.
Abstract
The tertiary structures of the S1 and S2 domains of the spike protein of the coronavirus which is responsible of the severe acute respiratory syndrome (SARS) have been recently predicted. Here a molecular assembly of SARS coronavirus peplomer which accounts for the available functional data is suggested. The interaction between S1 and S2 appears to be stabilised by a large hydrophobic network of aromatic side chains present in both domains. This feature results to be common to all coronaviruses, suggesting potential targeting for drugs preventing coronavirus-related infections.
Url:
DOI: 10.1016/j.bbrc.2004.10.156
PubMed: 15555555
PubMed Central: 7092937
Links to Exploration step
PMC:7092937Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Prediction of quaternary assembly of SARS coronavirus peplomer</title><author><name sortKey="Bernini, Andrea" sort="Bernini, Andrea" uniqKey="Bernini A" first="Andrea" last="Bernini">Andrea Bernini</name><affiliation><nlm:aff id="aff1">Department of Molecular Biology, Biomolecular Structure Research Center, University of Siena, I-53100 Siena, Italy</nlm:aff></affiliation></author><author><name sortKey="Spiga, Ottavia" sort="Spiga, Ottavia" uniqKey="Spiga O" first="Ottavia" last="Spiga">Ottavia Spiga</name><affiliation><nlm:aff id="aff1">Department of Molecular Biology, Biomolecular Structure Research Center, University of Siena, I-53100 Siena, Italy</nlm:aff></affiliation></author><author><name sortKey="Ciutti, Arianna" sort="Ciutti, Arianna" uniqKey="Ciutti A" first="Arianna" last="Ciutti">Arianna Ciutti</name><affiliation><nlm:aff id="aff1">Department of Molecular Biology, Biomolecular Structure Research Center, University of Siena, I-53100 Siena, Italy</nlm:aff></affiliation></author><author><name sortKey="Chiellini, Stefano" sort="Chiellini, Stefano" uniqKey="Chiellini S" first="Stefano" last="Chiellini">Stefano Chiellini</name><affiliation><nlm:aff id="aff1">Department of Molecular Biology, Biomolecular Structure Research Center, University of Siena, I-53100 Siena, Italy</nlm:aff></affiliation></author><author><name sortKey="Bracci, Luisa" sort="Bracci, Luisa" uniqKey="Bracci L" first="Luisa" last="Bracci">Luisa Bracci</name><affiliation><nlm:aff id="aff1">Department of Molecular Biology, Biomolecular Structure Research Center, University of Siena, I-53100 Siena, Italy</nlm:aff></affiliation></author><author><name sortKey="Yan, Xiyun" sort="Yan, Xiyun" uniqKey="Yan X" first="Xiyun" last="Yan">Xiyun Yan</name><affiliation><nlm:aff id="aff2">National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Zheng, Bojian" sort="Zheng, Bojian" uniqKey="Zheng B" first="Bojian" last="Zheng">Bojian Zheng</name><affiliation><nlm:aff id="aff3">Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Huang, Jiandong" sort="Huang, Jiandong" uniqKey="Huang J" first="Jiandong" last="Huang">Jiandong Huang</name><affiliation><nlm:aff id="aff4">Department of Biochemistry, The University of Hong Kong, Pokfulam, Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="He, Ming Liang" sort="He, Ming Liang" uniqKey="He M" first="Ming-Liang" last="He">Ming-Liang He</name><affiliation><nlm:aff id="aff5">Institute of Molecular Biology, The University of Hong Kong, Pokfulam, Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Song, Huai Dong" sort="Song, Huai Dong" uniqKey="Song H" first="Huai-Dong" last="Song">Huai-Dong Song</name><affiliation><nlm:aff id="aff6">State Key Laboratory for Medical Genomics, Shanghai, China</nlm:aff></affiliation></author><author><name sortKey="Hao, Pei" sort="Hao, Pei" uniqKey="Hao P" first="Pei" last="Hao">Pei Hao</name><affiliation><nlm:aff id="aff7">Shanghai Center for Bioinformation Technology, Shanghai, China</nlm:aff></affiliation></author><author><name sortKey="Zhao, Guoping" sort="Zhao, Guoping" uniqKey="Zhao G" first="Guoping" last="Zhao">Guoping Zhao</name><affiliation><nlm:aff id="aff8">Chinese National Human Genome Center at Shanghai, Shanghai, China</nlm:aff></affiliation></author><author><name sortKey="Niccolai, Neri" sort="Niccolai, Neri" uniqKey="Niccolai N" first="Neri" last="Niccolai">Neri Niccolai</name><affiliation><nlm:aff id="aff1">Department of Molecular Biology, Biomolecular Structure Research Center, University of Siena, I-53100 Siena, Italy</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">15555555</idno><idno type="pmc">7092937</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092937</idno><idno type="RBID">PMC:7092937</idno><idno type="doi">10.1016/j.bbrc.2004.10.156</idno><date when="2004">2004</date><idno type="wicri:Area/Pmc/Corpus">000E24</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000E24</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Prediction of quaternary assembly of SARS coronavirus peplomer</title><author><name sortKey="Bernini, Andrea" sort="Bernini, Andrea" uniqKey="Bernini A" first="Andrea" last="Bernini">Andrea Bernini</name><affiliation><nlm:aff id="aff1">Department of Molecular Biology, Biomolecular Structure Research Center, University of Siena, I-53100 Siena, Italy</nlm:aff></affiliation></author><author><name sortKey="Spiga, Ottavia" sort="Spiga, Ottavia" uniqKey="Spiga O" first="Ottavia" last="Spiga">Ottavia Spiga</name><affiliation><nlm:aff id="aff1">Department of Molecular Biology, Biomolecular Structure Research Center, University of Siena, I-53100 Siena, Italy</nlm:aff></affiliation></author><author><name sortKey="Ciutti, Arianna" sort="Ciutti, Arianna" uniqKey="Ciutti A" first="Arianna" last="Ciutti">Arianna Ciutti</name><affiliation><nlm:aff id="aff1">Department of Molecular Biology, Biomolecular Structure Research Center, University of Siena, I-53100 Siena, Italy</nlm:aff></affiliation></author><author><name sortKey="Chiellini, Stefano" sort="Chiellini, Stefano" uniqKey="Chiellini S" first="Stefano" last="Chiellini">Stefano Chiellini</name><affiliation><nlm:aff id="aff1">Department of Molecular Biology, Biomolecular Structure Research Center, University of Siena, I-53100 Siena, Italy</nlm:aff></affiliation></author><author><name sortKey="Bracci, Luisa" sort="Bracci, Luisa" uniqKey="Bracci L" first="Luisa" last="Bracci">Luisa Bracci</name><affiliation><nlm:aff id="aff1">Department of Molecular Biology, Biomolecular Structure Research Center, University of Siena, I-53100 Siena, Italy</nlm:aff></affiliation></author><author><name sortKey="Yan, Xiyun" sort="Yan, Xiyun" uniqKey="Yan X" first="Xiyun" last="Yan">Xiyun Yan</name><affiliation><nlm:aff id="aff2">National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Zheng, Bojian" sort="Zheng, Bojian" uniqKey="Zheng B" first="Bojian" last="Zheng">Bojian Zheng</name><affiliation><nlm:aff id="aff3">Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Huang, Jiandong" sort="Huang, Jiandong" uniqKey="Huang J" first="Jiandong" last="Huang">Jiandong Huang</name><affiliation><nlm:aff id="aff4">Department of Biochemistry, The University of Hong Kong, Pokfulam, Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="He, Ming Liang" sort="He, Ming Liang" uniqKey="He M" first="Ming-Liang" last="He">Ming-Liang He</name><affiliation><nlm:aff id="aff5">Institute of Molecular Biology, The University of Hong Kong, Pokfulam, Hong Kong, China</nlm:aff></affiliation></author><author><name sortKey="Song, Huai Dong" sort="Song, Huai Dong" uniqKey="Song H" first="Huai-Dong" last="Song">Huai-Dong Song</name><affiliation><nlm:aff id="aff6">State Key Laboratory for Medical Genomics, Shanghai, China</nlm:aff></affiliation></author><author><name sortKey="Hao, Pei" sort="Hao, Pei" uniqKey="Hao P" first="Pei" last="Hao">Pei Hao</name><affiliation><nlm:aff id="aff7">Shanghai Center for Bioinformation Technology, Shanghai, China</nlm:aff></affiliation></author><author><name sortKey="Zhao, Guoping" sort="Zhao, Guoping" uniqKey="Zhao G" first="Guoping" last="Zhao">Guoping Zhao</name><affiliation><nlm:aff id="aff8">Chinese National Human Genome Center at Shanghai, Shanghai, China</nlm:aff></affiliation></author><author><name sortKey="Niccolai, Neri" sort="Niccolai, Neri" uniqKey="Niccolai N" first="Neri" last="Niccolai">Neri Niccolai</name><affiliation><nlm:aff id="aff1">Department of Molecular Biology, Biomolecular Structure Research Center, University of Siena, I-53100 Siena, Italy</nlm:aff></affiliation></author></analytic><series><title level="j">Biochemical and Biophysical Research Communications</title><idno type="ISSN">0006-291X</idno><idno type="eISSN">1090-2104</idno><imprint><date when="2004">2004</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The tertiary structures of the S1 and S2 domains of the spike protein of the coronavirus which is responsible of the severe acute respiratory syndrome (SARS) have been recently predicted. Here a molecular assembly of SARS coronavirus peplomer which accounts for the available functional data is suggested. The interaction between S1 and S2 appears to be stabilised by a large hydrophobic network of aromatic side chains present in both domains. This feature results to be common to all coronaviruses, suggesting potential targeting for drugs preventing coronavirus-related infections.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Brown, E G" uniqKey="Brown E">E.G. Brown</name></author><author><name sortKey="Tetro, J A" uniqKey="Tetro J">J.A. Tetro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, H" uniqKey="Yang H">H. Yang</name></author><author><name sortKey="Yang, M" uniqKey="Yang M">M. Yang</name></author><author><name sortKey="Ding, Y" uniqKey="Ding Y">Y. Ding</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y. Liu</name></author><author><name sortKey="Lou, Z" uniqKey="Lou Z">Z. Lou</name></author><author><name sortKey="Zhou, Z" uniqKey="Zhou Z">Z. Zhou</name></author><author><name sortKey="Sun, L" uniqKey="Sun L">L. Sun</name></author><author><name sortKey="Mo, L" uniqKey="Mo L">L. Mo</name></author><author><name sortKey="Ye, S" uniqKey="Ye S">S. Ye</name></author><author><name sortKey="Pang, H" uniqKey="Pang H">H. Pang</name></author><author><name sortKey="Gao, G F" uniqKey="Gao G">G.F. Gao</name></author><author><name sortKey="Anand, K" uniqKey="Anand K">K. Anand</name></author><author><name sortKey="Bartlam, M" uniqKey="Bartlam M">M. Bartlam</name></author><author><name sortKey="Hilgenfeld, R" uniqKey="Hilgenfeld R">R. Hilgenfeld</name></author><author><name sortKey="Rao, Z" uniqKey="Rao Z">Z. Rao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Egloff, M P" uniqKey="Egloff M">M.P. Egloff</name></author><author><name sortKey="Ferron, F" uniqKey="Ferron F">F. Ferron</name></author><author><name sortKey="Campanacci, V" uniqKey="Campanacci V">V. Campanacci</name></author><author><name sortKey="Longhi, S" uniqKey="Longhi S">S. Longhi</name></author><author><name sortKey="Rancurel, C" uniqKey="Rancurel C">C. Rancurel</name></author><author><name sortKey="Dutartre, H" uniqKey="Dutartre H">H. Dutartre</name></author><author><name sortKey="Snijder, E J" uniqKey="Snijder E">E.J. Snijder</name></author><author><name sortKey="Gorbalenya, A E" uniqKey="Gorbalenya A">A.E. Gorbalenya</name></author><author><name sortKey="Cambillau, C" uniqKey="Cambillau C">C. Cambillau</name></author><author><name sortKey="Canard, B" uniqKey="Canard B">B. Canard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shen, X" uniqKey="Shen X">X. Shen</name></author><author><name sortKey="Xue, J H" uniqKey="Xue J">J.H. Xue</name></author><author><name sortKey="Yu, C Y" uniqKey="Yu C">C.Y. Yu</name></author><author><name sortKey="Luo, H B" uniqKey="Luo H">H.B. Luo</name></author><author><name sortKey="Qin, L" uniqKey="Qin L">L. Qin</name></author><author><name sortKey="Yu, X J" uniqKey="Yu X">X.J. Yu</name></author><author><name sortKey="Chen, J" uniqKey="Chen J">J. Chen</name></author><author><name sortKey="Chen, L L" uniqKey="Chen L">L.L. Chen</name></author><author><name sortKey="Xiong, B" uniqKey="Xiong B">B. Xiong</name></author><author><name sortKey="Yue, L D" uniqKey="Yue L">L.D. Yue</name></author><author><name sortKey="Cai, J H" uniqKey="Cai J">J.H. Cai</name></author><author><name sortKey="Shen, J H" uniqKey="Shen J">J.H. Shen</name></author><author><name sortKey="Luo, X M" uniqKey="Luo X">X.M. Luo</name></author><author><name sortKey="Chen, K X" uniqKey="Chen K">K.X. Chen</name></author><author><name sortKey="Shi, T L" uniqKey="Shi T">T.L. Shi</name></author><author><name sortKey="Li, Y X" uniqKey="Li Y">Y.X. Li</name></author><author><name sortKey="Hu, G X" uniqKey="Hu G">G.X. Hu</name></author><author><name sortKey="Jiang, H L" uniqKey="Jiang H">H.L. Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Spiga, O" uniqKey="Spiga O">O. Spiga</name></author><author><name sortKey="Bernini, A" uniqKey="Bernini A">A. Bernini</name></author><author><name sortKey="Ciutti, A" uniqKey="Ciutti A">A. Ciutti</name></author><author><name sortKey="Chiellini, S" uniqKey="Chiellini S">S. Chiellini</name></author><author><name sortKey="Menciassi, N" uniqKey="Menciassi N">N. Menciassi</name></author><author><name sortKey="Finetti, F" uniqKey="Finetti F">F. Finetti</name></author><author><name sortKey="Causarono, V" uniqKey="Causarono V">V. Causarono</name></author><author><name sortKey="Anselmi, F" uniqKey="Anselmi F">F. Anselmi</name></author><author><name sortKey="Prischi, F" uniqKey="Prischi F">F. Prischi</name></author><author><name sortKey="Niccolai, N" uniqKey="Niccolai N">N. Niccolai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, X" uniqKey="Xu X">X. Xu</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y. Liu</name></author><author><name sortKey="Weiss, S" uniqKey="Weiss S">S. Weiss</name></author><author><name sortKey="Arnold, E" uniqKey="Arnold E">E. Arnold</name></author><author><name sortKey="Sarafianos, S G" uniqKey="Sarafianos S">S.G. Sarafianos</name></author><author><name sortKey="Ding, J" uniqKey="Ding J">J. Ding</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cavanagh, D" uniqKey="Cavanagh D">D. Cavanagh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, Y" uniqKey="Lin Y">Y. Lin</name></author><author><name sortKey="Yan, X" uniqKey="Yan X">X. Yan</name></author><author><name sortKey="Cao, W" uniqKey="Cao W">W. Cao</name></author><author><name sortKey="Wang, C" uniqKey="Wang C">C. Wang</name></author><author><name sortKey="Feng, J" uniqKey="Feng J">J. Feng</name></author><author><name sortKey="Duan, J" uniqKey="Duan J">J. Duan</name></author><author><name sortKey="Xie, S" uniqKey="Xie S">S. Xie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Groot, R J" uniqKey="De Groot R">R.J. de Groot</name></author><author><name sortKey="Luytjes, W" uniqKey="Luytjes W">W. Luytjes</name></author><author><name sortKey="Horzinek, M C" uniqKey="Horzinek M">M.C. Horzinek</name></author><author><name sortKey="Van Der Zeijst, B A" uniqKey="Van Der Zeijst B">B.A. van der Zeijst</name></author><author><name sortKey="Spaan, W J" uniqKey="Spaan W">W.J. Spaan</name></author><author><name sortKey="Lenstra, J A" uniqKey="Lenstra J">J.A. Lenstra</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Berman, H M" uniqKey="Berman H">H.M. Berman</name></author><author><name sortKey="Westbrook, J" uniqKey="Westbrook J">J. Westbrook</name></author><author><name sortKey="Feng, Z" uniqKey="Feng Z">Z. Feng</name></author><author><name sortKey="Gilliland, G" uniqKey="Gilliland G">G. Gilliland</name></author><author><name sortKey="Bhat, T N" uniqKey="Bhat T">T.N. Bhat</name></author><author><name sortKey="Weissig, H" uniqKey="Weissig H">H. Weissig</name></author><author><name sortKey="Shindyalov, I N" uniqKey="Shindyalov I">I.N. Shindyalov</name></author><author><name sortKey="Bourne, P E" uniqKey="Bourne P">P.E. Bourne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sippl, M J" uniqKey="Sippl M">M.J. Sippl</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Berendsen, H J C" uniqKey="Berendsen H">H.J.C. Berendsen</name></author><author><name sortKey="Van Der Spoel, D" uniqKey="Van Der Spoel D">D. van der Spoel</name></author><author><name sortKey="Van Drunen, R" uniqKey="Van Drunen R">R. van Drunen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Koradi, R" uniqKey="Koradi R">R. Koradi</name></author><author><name sortKey="Billeter, M" uniqKey="Billeter M">M. Billeter</name></author><author><name sortKey="Wuthrich, K" uniqKey="Wuthrich K">K. Wuthrich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lewicki, D N" uniqKey="Lewicki D">D.N. Lewicki</name></author><author><name sortKey="Gallagher, T M" uniqKey="Gallagher T">T.M. Gallagher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wong, S K" uniqKey="Wong S">S.K. Wong</name></author><author><name sortKey="Li, W" uniqKey="Li W">W. Li</name></author><author><name sortKey="Moore, M J" uniqKey="Moore M">M.J. Moore</name></author><author><name sortKey="Choe, H" uniqKey="Choe H">H. Choe</name></author><author><name sortKey="Farzan, M" uniqKey="Farzan M">M. Farzan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thompson, J D" uniqKey="Thompson J">J.D. Thompson</name></author><author><name sortKey="Higgins, D G" uniqKey="Higgins D">D.G. Higgins</name></author><author><name sortKey="Gibson, T J" uniqKey="Gibson T">T.J. Gibson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sauter, N K" uniqKey="Sauter N">N.K. Sauter</name></author><author><name sortKey="Hanson, J E" uniqKey="Hanson J">J.E. Hanson</name></author><author><name sortKey="Glick, G D" uniqKey="Glick G">G.D. Glick</name></author><author><name sortKey="Brown, J H" uniqKey="Brown J">J.H. Brown</name></author><author><name sortKey="Crowther, R L" uniqKey="Crowther R">R.L. Crowther</name></author><author><name sortKey="Park, S J" uniqKey="Park S">S.J. Park</name></author><author><name sortKey="Skehel, J J" uniqKey="Skehel J">J.J. Skehel</name></author><author><name sortKey="Wiley, D C" uniqKey="Wiley D">D.C. Wiley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Delmas, B" uniqKey="Delmas B">B. Delmas</name></author><author><name sortKey="Laude, H" uniqKey="Laude H">H. Laude</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wolf, E" uniqKey="Wolf E">E. Wolf</name></author><author><name sortKey="Kim, P S" uniqKey="Kim P">P.S. Kim</name></author><author><name sortKey="Berger, B" uniqKey="Berger B">B. Berger</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Kyte, J" uniqKey="Kyte J">J. Kyte</name></author><author><name sortKey="Doolittle, R F" uniqKey="Doolittle R">R.F. Doolittle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhu, J" uniqKey="Zhu J">J. Zhu</name></author><author><name sortKey="Xiao, G" uniqKey="Xiao G">G. Xiao</name></author><author><name sortKey="Xu, Y" uniqKey="Xu Y">Y. Xu</name></author><author><name sortKey="Yuan, F" uniqKey="Yuan F">F. Yuan</name></author><author><name sortKey="Zheng, C" uniqKey="Zheng C">C. Zheng</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y. Liu</name></author><author><name sortKey="Yan, H" uniqKey="Yan H">H. Yan</name></author><author><name sortKey="Cole, D K" uniqKey="Cole D">D.K. Cole</name></author><author><name sortKey="Bell, J I" uniqKey="Bell J">J.I. Bell</name></author><author><name sortKey="Rao, Z" uniqKey="Rao Z">Z. Rao</name></author><author><name sortKey="Tien, P" uniqKey="Tien P">P. Tien</name></author><author><name sortKey="Gao, G F" uniqKey="Gao G">G.F. Gao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, S" uniqKey="Liu S">S. Liu</name></author><author><name sortKey="Xiao, G" uniqKey="Xiao G">G. Xiao</name></author><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y. Chen</name></author><author><name sortKey="He, Y" uniqKey="He Y">Y. He</name></author><author><name sortKey="Niu, J" uniqKey="Niu J">J. Niu</name></author><author><name sortKey="Escalante, C R" uniqKey="Escalante C">C.R. Escalante</name></author><author><name sortKey="Xiong, H" uniqKey="Xiong H">H. Xiong</name></author><author><name sortKey="Farmar, J" uniqKey="Farmar J">J. Farmar</name></author><author><name sortKey="Debnath, A K" uniqKey="Debnath A">A.K. Debnath</name></author><author><name sortKey="Tien, P" uniqKey="Tien P">P. Tien</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S. Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, Y" uniqKey="Xu Y">Y. Xu</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y. Liu</name></author><author><name sortKey="Lou, Z" uniqKey="Lou Z">Z. Lou</name></author><author><name sortKey="Qin, L" uniqKey="Qin L">L. Qin</name></author><author><name sortKey="Li, X" uniqKey="Li X">X. Li</name></author><author><name sortKey="Bai, Z" uniqKey="Bai Z">Z. Bai</name></author><author><name sortKey="Pang, H" uniqKey="Pang H">H. Pang</name></author><author><name sortKey="Tien, P" uniqKey="Tien P">P. Tien</name></author><author><name sortKey="Gao, G F" uniqKey="Gao G">G.F. Gao</name></author><author><name sortKey="Rao, Z" uniqKey="Rao Z">Z. Rao</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Biochem Biophys Res Commun</journal-id><journal-id journal-id-type="iso-abbrev">Biochem. Biophys. Res. Commun</journal-id><journal-title-group><journal-title>Biochemical and Biophysical Research Communications</journal-title></journal-title-group><issn pub-type="ppub">0006-291X</issn><issn pub-type="epub">1090-2104</issn><publisher><publisher-name>Elsevier Inc.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">15555555</article-id><article-id pub-id-type="pmc">7092937</article-id><article-id pub-id-type="publisher-id">S0006-291X(04)02463-5</article-id><article-id pub-id-type="doi">10.1016/j.bbrc.2004.10.156</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Prediction of quaternary assembly of SARS coronavirus peplomer</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Bernini</surname><given-names>Andrea</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Spiga</surname><given-names>Ottavia</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Ciutti</surname><given-names>Arianna</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Chiellini</surname><given-names>Stefano</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Bracci</surname><given-names>Luisa</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Yan</surname><given-names>Xiyun</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author"><name><surname>Zheng</surname><given-names>Bojian</given-names></name><xref rid="aff3" ref-type="aff">c</xref></contrib><contrib contrib-type="author"><name><surname>Huang</surname><given-names>Jiandong</given-names></name><xref rid="aff4" ref-type="aff">d</xref></contrib><contrib contrib-type="author"><name><surname>He</surname><given-names>Ming-Liang</given-names></name><xref rid="aff5" ref-type="aff">e</xref></contrib><contrib contrib-type="author"><name><surname>Song</surname><given-names>Huai-Dong</given-names></name><xref rid="aff6" ref-type="aff">f</xref></contrib><contrib contrib-type="author"><name><surname>Hao</surname><given-names>Pei</given-names></name><xref rid="aff7" ref-type="aff">g</xref></contrib><contrib contrib-type="author"><name><surname>Zhao</surname><given-names>Guoping</given-names></name><xref rid="aff8" ref-type="aff">h</xref></contrib><contrib contrib-type="author"><name><surname>Niccolai</surname><given-names>Neri</given-names></name><email>niccolai@unisi.it</email><xref rid="aff1" ref-type="aff">a</xref><xref rid="cor1" ref-type="corresp">*</xref></contrib></contrib-group><aff id="aff1"><label>a</label>Department of Molecular Biology, Biomolecular Structure Research Center, University of Siena, I-53100 Siena, Italy</aff><aff id="aff2"><label>b</label>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China</aff><aff id="aff3"><label>c</label>Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong, China</aff><aff id="aff4"><label>d</label>Department of Biochemistry, The University of Hong Kong, Pokfulam, Hong Kong, China</aff><aff id="aff5"><label>e</label>Institute of Molecular Biology, The University of Hong Kong, Pokfulam, Hong Kong, China</aff><aff id="aff6"><label>f</label>State Key Laboratory for Medical Genomics, Shanghai, China</aff><aff id="aff7"><label>g</label>Shanghai Center for Bioinformation Technology, Shanghai, China</aff><aff id="aff8"><label>h</label>Chinese National Human Genome Center at Shanghai, Shanghai, China</aff><author-notes><corresp id="cor1"><label>*</label>Corresponding author. Fax: +39 577 234903 <email>niccolai@unisi.it</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>11</day><month>11</month><year>2004</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><day>24</day><month>12</month><year>2004</year></pub-date><pub-date pub-type="epub"><day>11</day><month>11</month><year>2004</year></pub-date><volume>325</volume><issue>4</issue><fpage>1210</fpage><lpage>1214</lpage><history><date date-type="received"><day>13</day><month>10</month><year>2004</year></date></history><permissions><copyright-statement>Copyright © 2004 Elsevier Inc. All rights reserved.</copyright-statement><copyright-year>2004</copyright-year><copyright-holder>Elsevier Inc.</copyright-holder><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions><abstract><p>The tertiary structures of the S1 and S2 domains of the spike protein of the coronavirus which is responsible of the severe acute respiratory syndrome (SARS) have been recently predicted. Here a molecular assembly of SARS coronavirus peplomer which accounts for the available functional data is suggested. The interaction between S1 and S2 appears to be stabilised by a large hydrophobic network of aromatic side chains present in both domains. This feature results to be common to all coronaviruses, suggesting potential targeting for drugs preventing coronavirus-related infections.</p></abstract><kwd-group><title>Keywords</title><kwd>SARS coronavirus</kwd><kwd>Spike glycoprotein</kwd><kwd>Quaternary structure prediction</kwd></kwd-group></article-meta></front><body><p id="para.0010">We are now in a post-epidemic period of the severe acute respiratory syndrome (SARS), caused by the coronavirus henceforth called SARS-CoV. Nevertheless, since the mode of transmission, spread, and mechanisms of virulence of SARS-CoV are not fully understood, all the possible weapons that Immunology and Pharmacology can provide should be prepared against the virus to defend ourselves better when this virus will rear again its infecting crown <xref rid="bib1" ref-type="bibr">[1]</xref>.</p><p id="para.0015">For a pharmacological approach the structural characterisation of the molecular repertoire of the target organism is of fundamental importance . In this respect, not much is available yet for SARS-CoV, as only two crystallographic determinations <xref rid="bib2" ref-type="bibr">[2]</xref>, <xref rid="bib3" ref-type="bibr">[3]</xref> and few predictive models <xref rid="bib4" ref-type="bibr">[4]</xref>, <xref rid="bib5" ref-type="bibr">[5]</xref>, <xref rid="bib6" ref-type="bibr">[6]</xref> are so far available.</p><p id="para.0020">Among the above-mentioned structures, the predicted structures of S1 and S2 domains of the viral spike glycoprotein <xref rid="bib5" ref-type="bibr">[5]</xref> can represent a rational basis to design specific antiviral drugs and diagnostic kits. This protein, indeed, has been found to be the viral membrane protein responsible of SARS-CoV cell entry by interacting with the receptor of the target cell and causing subsequent virus-cell fusion <xref rid="bib7" ref-type="bibr">[7]</xref>.</p><p id="para.0025">SARS-CoV ultra-high resolution images have been obtained <xref rid="bib8" ref-type="bibr">[8]</xref> by scanning electron microscopy, SEM, which indicate that the spike glycoprotein is organised as a trimer. This finding offers a fundamental hint to investigate the overall assembly of the outer viral particles, peplomers, which give that characteristic crown-like aspect to the virion, therefore classified in the <italic>coronaviridae</italic> family <xref rid="bib9" ref-type="bibr">[9]</xref>.</p><p id="para.0030">A stable quaternary structure without covalent cross-linking has been proposed, in general, for coronavirus peplomers <xref rid="bib7" ref-type="bibr">[7]</xref>. This feature is consistent with our previous structural predictions, as no Cys residue without a corresponding cystine-bridged counterpart is present in both models of SARS-CoV spike glycoprotein domains.</p><p id="para.0035">The distribution of N-glycosylation and mutation sites has also been considered for a fine-tuning of the peplomer structural features with functional data.</p><sec id="section.0010"><title>Materials and methods</title><p id="para.0040">Peplomer model building has been performed on the basis of the structures of the S1 and S2 domains of the SARS-CoV spike protein which are available in the Protein Data Bank <xref rid="bib10" ref-type="bibr">[10]</xref>: the structure models 1Q4Z and 1U4K have been used for S1 and S2, respectively. Docking of the two domains has been manually performed and the reliability of each of the possible peplomer assemblies has been discussed according to the ProsaII software package <xref rid="bib11" ref-type="bibr">[11]</xref>. Accordingly, quaternary structures exhibiting the lowest energies for atom pair and solvent interaction were considered for further optimisation by using molecular dynamics simulations with Gromacs <xref rid="bib12" ref-type="bibr">[12]</xref>. After a PROCHECK analysis of the final refined peplomer structure it has been deposited in the Protein Data Bank with the ID code 1T7G. All displays of structures, as well as exposed surface area (ESA) calculations, were carried out with the program MOLMOL <xref rid="bib13" ref-type="bibr">[13]</xref>.</p></sec><sec id="section.0015"><title>Results and discussion</title><p id="para.0045">SARS coronavirus peplomer shape and dimensions are now well defined by recent SEM determinations <xref rid="bib8" ref-type="bibr">[8]</xref>, and the club-shaped protrusions of a trimer glycoprotein appear to extend itself approximately 200 Å from the virion envelope membrane with a maximum width of 100–200 Å.</p><p id="para.0050">It has been shown that coronaviruses present the S1 domain as the globular head of the spike with receptor-binding activity and that the S2 domain is present in the stalk portion of the spike <xref rid="bib14" ref-type="bibr">[14]</xref>. In this respect, the fact that SEM images clearly suggest that in the viral peplomers the spike glycoprotein is present as a trimer <xref rid="bib8" ref-type="bibr">[8]</xref> results to be a fundamental starting point for our model building procedure. This is also in accord with the general rule that coronavirus spike proteins form three-stranded left-handed coiled-coils. Moreover, the fact that the 320–518 fragment of S1 domain has been identified as the SARS-CoV peplomer binding site to the ACE2 cellular receptor <xref rid="bib15" ref-type="bibr">[15]</xref> implies that the residues which are the most involved in the interaction with the receptor have to be positioned in the S1 external top side.</p><p id="para.0055">These first morphological and functional hints have been coupled to the results of a systematic search for surface hot spots of S1 and S2 SARS-CoV domains, i.e., potential drug binding and/or protein–protein interaction sites, to gain structural information on the relative orientations of these S1 and S2 domains. This analysis has been performed on the basis of S1 and S2 molecular models available <xref rid="bib5" ref-type="bibr">[5]</xref>. Furthermore, a Clustal W <xref rid="bib16" ref-type="bibr">[16]</xref> analysis of all the coronavirus spike proteins present in the SwissProt protein sequence data bank has been carried out and 236 sequences have been found to be compared with the one of SARS-CoV, SwissProt Accession No. <ext-link ext-link-type="gen" xlink:href="P59594">P59594</ext-link>, originally used for our model building of the S1 and S2 domains of the S glycoprotein.</p><p id="para.0060">To build the molecular model of the SARS-CoV peplomer, the modelled structures of its S1 and S2 domains have been used together with homology criteria with the quaternary assembly of other viral systems <xref rid="bib14" ref-type="bibr">[14]</xref>, <xref rid="bib17" ref-type="bibr">[17]</xref>, <xref rid="bib18" ref-type="bibr">[18]</xref>.</p><p id="para.0065">In the first step of the model building procedure, the positioning of each of the three S2 in respect to the others was carried out by assembling the long α-helix spanning residues 904–968, constituting the first heptad repeat (HR1, according to the prediction by Multicoil <xref rid="bib19" ref-type="bibr">[19]</xref>), in a three-stranded, left-handed coiled-coil. The three HR1s were first aligned parallel along the major axis, and then rotated about the center of mass of the same amount to get the amino acids of positions <italic>a</italic> and <italic>d</italic> justaxposed. The structure was refined by minimizaton followed by a simulated annealing dynamics.</p><p id="para.0070">In the second step, possible interfaces between the S1 and S2 domains, and among the S1 + S2 components, needed for the assembly of a trimeric structure, have been systematically searched.</p><p id="para.0075">Thus, in spite of the limited sequence homology, ranging from 20.39% to 27.63%, found for all these spike glycoproteins, in the S1 hydrophobic pocket delimited by F187, F334, F253, and W423 a high level of residue conservation is present. In this respect SARS-CoV, when compared with all the other coronaviruses, is unique in its W/F swapping between position 253 and 423, see <xref rid="tbl1" ref-type="table">Table 1</xref>. From <xref rid="tbl1" ref-type="table">Table 1</xref> it can also be noticed that in the S2 domain the hydrophobic residues L803 and F805, totally conserved among the SARS-CoV available genomes and fully exposed in the S2 molecular model, are located in a sequence position where only hydrophobic residues are found.<table-wrap position="float" id="tbl1"><label>Table 1</label><caption><p>Amino acid occupancy of a possible strong binding site between S1 and S2 domains</p></caption><table frame="hsides" rules="groups"><thead><tr><th>Coronavirus</th><th>Number of sequenced genomes</th><th>187</th><th>253</th><th>334</th><th>423</th><th>782</th><th>784</th></tr></thead><tbody><tr><td>Human sars</td><td align="char">36</td><td>F</td><td>F</td><td>F</td><td>W</td><td>L</td><td>F</td></tr><tr><td>Murine</td><td align="char">16</td><td>F</td><td>W</td><td>F,V</td><td>Y</td><td>L,V</td><td>F</td></tr><tr><td>Porcine(1)</td><td align="char">1</td><td>F</td><td>W</td><td>V</td><td>Y</td><td>L</td><td>F</td></tr><tr><td>Porcine(2)</td><td align="char">16</td><td>F</td><td>W</td><td>V</td><td>Y</td><td>L</td><td>F</td></tr><tr><td>Porcine(3)</td><td align="char">30</td><td>F</td><td>W</td><td>V</td><td>Y</td><td>L</td><td>F</td></tr><tr><td>Porcine(4)</td><td align="char">7</td><td>F</td><td>W</td><td>V</td><td>Y</td><td>L</td><td>F</td></tr><tr><td>Bovine</td><td align="char">26</td><td>Y</td><td>W</td><td>V</td><td>Y</td><td>L</td><td>F</td></tr><tr><td>Human</td><td align="char">24</td><td>F</td><td>W</td><td>V</td><td>Y</td><td>L,I</td><td>F</td></tr><tr><td>Equine</td><td align="char">1</td><td>Y</td><td>W</td><td>V</td><td>Y</td><td>L</td><td>F</td></tr><tr><td>Avian</td><td align="char">112</td><td>F</td><td>W</td><td>V</td><td>Y</td><td>L,I,V</td><td>F</td></tr><tr><td>Feline</td><td align="char">54</td><td>F</td><td>W</td><td>V</td><td>Y</td><td>L</td><td>F</td></tr><tr><td>Canine</td><td align="char">8</td><td>Y</td><td>W</td><td>V</td><td>Y</td><td>L</td><td>F</td></tr></tbody></table><table-wrap-foot><fn><p>(1), Hemagglutinating encephalomyelitis virus; (2), transmissible gastroenteritis virus; (3), respiratory virus; and (4), epidemic diarrhea virus.</p></fn></table-wrap-foot></table-wrap></p><p id="para.0080">The large difference in the pathologies induced by coronavirus infections suggests that a role for these two hydrophobic moieties of S1 and S2 domains might be attributed to the peplomer assembly rather than to the interaction with the host cell. Residues F187, F334, F253, and W423 could, indeed, form the S1 hydrophobic pocket where S2 puts its hydrophobic finger formed by L803 and F805 residues.</p><p id="para.0085">The remarkable agreement between the steric requirements for the S1–S2 interaction and the surface position of the proposed S1 binding site to the ACE2 receptor points towards a finite orientation of these peplomeric domains, see <xref rid="fig1" ref-type="fig">Fig. 1</xref>. From this starting point, to recompose the full SARS-CoV peplomer from its components, we used the following simple criteria: (i) orienting each S1 and the S2 stalk domains so that they could dock through the interaction described above, (ii) keeping all the potential N-glycosylation sites as surface exposed as possible, and (iii) positioning the largest hydrophobic surface patches in subunit interfaces. The fact that in the S2 trimer the side chains of L803 and F805 residues are still surface accessible after the coiled coil formation supports the hypothesis that the peplomer reaches its structural stability through the hydrophobic interactions of the S1 pocket with the S2 finger, as depicted in <xref rid="fig2" ref-type="fig">Fig. 2</xref>. Then, geometrical and energetic considerations converge towards possible solutions for the structure of the SARS-CoV peplomer. In <xref rid="fig3" ref-type="fig">Fig. 3</xref>, three molecules of S1–S2 adducts are positioned after their assembly, in a way which is consistent with the overall size of the peplomer <xref rid="bib8" ref-type="bibr">[8]</xref>. It should be noted also that, among the mutations which have been found in the SARS-CoV spike protein region of all the available genomes, see <xref rid="tbl2" ref-type="table">Table 2</xref>, nothing occurs in the S1–S2 interfaces here identified.<fig id="fig1"><label>Fig. 1</label><caption><p>The S1 domain oriented to fit the morphological SEM images of <xref rid="bib8" ref-type="bibr">[8]</xref>. In yellow and in red the potential N-glycosylation sites and the residues involved in the interaction with ACE2 <xref rid="bib15" ref-type="bibr">[15]</xref> are, respectively, colored. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this paper.)</p></caption><graphic xlink:href="gr1"></graphic></fig><fig id="fig2"><label>Fig. 2</label><caption><p>A detailed representation of the S1 (dark blue) hydrophobic pocket interacting with the S2 (pale blue) finger. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this paper.)</p></caption><graphic xlink:href="gr2"></graphic></fig><fig id="fig3"><label>Fig. 3</label><caption><p>Three spike glycoproteins form the peplomer of SARS-CoV coronavirus.</p></caption><graphic xlink:href="gr3"></graphic></fig><table-wrap position="float" id="tbl2"><label>Table 2</label><caption><p>Mutation site topology occurring in all the available strains of SARS-CoV spike glycoprotein</p></caption><table frame="hsides" rules="groups"><thead><tr><th>aa</th><th>Mutation topology</th><th>TOR2</th><th>BJ01</th><th>HZS2_C</th><th>CUHK_LC2</th><th>SOD</th><th>HZS2_FC</th><th>GZ_A</th><th>HGZ8L1_A</th></tr></thead><tbody><tr><td align="char">49</td><td>Exposed top</td><td>S</td><td>S</td><td>S</td><td>S</td><td>S</td><td>S</td><td>L</td><td>S</td></tr><tr><td align="char">74</td><td>Exposed top</td><td>H</td><td>H</td><td>H</td><td>H</td><td>H</td><td>H</td><td>H</td><td>F</td></tr><tr><td align="char">75</td><td>Exposed top</td><td>T</td><td>T</td><td>T</td><td>T</td><td>T</td><td>T</td><td>R</td><td>T</td></tr><tr><td align="char">77</td><td>Exposed top</td><td>G</td><td>D</td><td>D</td><td>G</td><td>G</td><td>G</td><td>D</td><td>D</td></tr><tr><td align="char">239</td><td>Partially exposed side</td><td>S</td><td>S</td><td>S</td><td>S</td><td>S</td><td>S</td><td>S</td><td>L</td></tr><tr><td align="char">244</td><td>Buried</td><td>I</td><td>T</td><td>T</td><td>I</td><td>I</td><td>I</td><td>T</td><td>T</td></tr><tr><td align="char">311</td><td>Exposed side</td><td>G</td><td>G</td><td>G</td><td>G</td><td>G</td><td>G</td><td>G</td><td>R</td></tr><tr><td align="char">344</td><td>Partially exposed side</td><td>K</td><td>K</td><td>K</td><td>K</td><td>K</td><td>K</td><td>K</td><td>R</td></tr><tr><td align="char">577</td><td>Buried, interface S1-S1</td><td>A</td><td>S</td><td>S</td><td>S</td><td>S</td><td>S</td><td>S</td><td>S</td></tr><tr><td align="char">778</td><td>Buried</td><td>Y</td><td>Y</td><td>Y</td><td>Y</td><td>Y</td><td>Y</td><td>D</td><td>D</td></tr><tr><td align="char">1148</td><td>Exposed down</td><td>L</td><td>L</td><td>L</td><td>L</td><td>F</td><td>F</td><td>L</td><td>L</td></tr><tr><td align="char">1179</td><td>Buried</td><td>L</td><td>L</td><td>L</td><td>L</td><td>L</td><td>L</td><td>L</td><td>F</td></tr><tr><td align="char">1208</td><td>Non-modelled</td><td>A</td><td>A</td><td>A</td><td>V</td><td>A</td><td>A</td><td>A</td><td>A</td></tr></tbody></table></table-wrap></p><p id="para.0090">For the S2 moiety of the S glycoprotein, composed by one well-structured moiety containing the HR1 and another subdomain spanning the 1027–1195 segment of S glycoprotein and containing the HR2 (residues 1148–1193), ambiguity remains on the structure and on the location of the second in the peplomer structure. Such subdomain is critical for the interaction with the viral envelope, due to its proximity to the <italic>trans</italic>-membrane region and for the overall structure stability of the peplomer. In fact, a peptide reproducing the C terminal heptad repeat fragment 1161–1187 of S2 exhibits antiviral activity <xref rid="bib20" ref-type="bibr">[20]</xref>.</p><p id="para.0095">Thus, 94% of SARS-CoV peplomer structure has been modelled and deposited with the pdb ID code 1T7G. Accordingly, the most interesting regions to be reproduced in synthetic peptides for mimotope design have been found, as well as the hydrophobic sites distributed at the S1/S1, S2/S2, and S1/S2 interfaces for targeting of potential antiviral drugs (patent RM2004A000162). The fact that we could not model the 665–736 sequence of the S glycoprotein does not interfere with the exposed surface on top of the SARS-CoV peplomer, as the missing modelled moiety can be identified in a peplomer lateral region, where a deep groove is found. This peplomer region could be filled by the non-modelled part of the sequence, which consistently exhibits an extensive hydrophobic character <xref rid="bib21" ref-type="bibr">[21]</xref>. In the present peplomer model, the so-called HR1 and HR2 moieties, i.e., the N and C terminal heptad repeat regions, respectively, spanning the sequences 904–975 and 1148–1193, are not bound together. This feature is consistent with the extensive conformational change, necessary for this and several other viruses for the fusogenic mechanism <xref rid="bib22" ref-type="bibr">[22]</xref>, <xref rid="bib23" ref-type="bibr">[23]</xref>, <xref rid="bib24" ref-type="bibr">[24]</xref>.</p><p id="para.0100">Then, on the basis of the obtained peplomer structure, correlations can be explored between viral genome mutations and possible interactions with the host cell receptor(s). As reported in <xref rid="tbl2" ref-type="table">Table 2</xref>, on the basis of the proposed quaternary assembly a systematic topological analysis of mutation sites occurring in the 36 genomes so far available for the SARS-CoV spike glycoprotein has been done. It can be observed that (i) most of the mutations are found in exposed sites; (ii) the only mutation involving a relevant position for the receptor interaction, i.e., 344 K/R, is a conservative one; and (iii) non-conservative substitutions are found in the buried positions of residue 778 with Y/D, which do not induce sterical conflicts.</p><p id="para.0105">The structural characterisation of SARS-CoV spike glycoprotein domains, here described, suggests also a general scheme for the peplomer assembly of all coronaviruses. In fact, from the sequence alignment of the spike glycoproteins of all known coronaviruses, as shown in <xref rid="tbl1" ref-type="table">Table 1</xref>, it appears that the above-described hydrophobic interaction between the S1 pocket and the S2 finger is very conserved. It could, therefore, represent a very critical region for the interaction between S1 and S2 domains for all coronaviruses, opening new perspectives for the design of small molecules that can efficiently interfere with the viral replication. Hence, SARS as well as all the other members of the <italic>coronaviridae</italic> family could put down their infecting crown with the same type of antiviral drug, which could protect from possible transmission of coronavirus infections from wild animals.</p></sec></body><back><ref-list id="bibliography.0010"><title>References</title><ref id="bib1"><label>1</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Brown</surname><given-names>E.G.</given-names></name><name><surname>Tetro</surname><given-names>J.A.</given-names></name></person-group><article-title>Comparative analysis of the SARS coronavirus genome: a good start to a long journey</article-title><source>Lancet</source><volume>361</volume><year>2003</year><fpage>1756</fpage><lpage>1757</lpage><pub-id pub-id-type="pmid">12781529</pub-id></element-citation></ref><ref id="bib2"><label>2</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yang</surname><given-names>H.</given-names></name><name><surname>Yang</surname><given-names>M.</given-names></name><name><surname>Ding</surname><given-names>Y.</given-names></name><name><surname>Liu</surname><given-names>Y.</given-names></name><name><surname>Lou</surname><given-names>Z.</given-names></name><name><surname>Zhou</surname><given-names>Z.</given-names></name><name><surname>Sun</surname><given-names>L.</given-names></name><name><surname>Mo</surname><given-names>L.</given-names></name><name><surname>Ye</surname><given-names>S.</given-names></name><name><surname>Pang</surname><given-names>H.</given-names></name><name><surname>Gao</surname><given-names>G.F.</given-names></name><name><surname>Anand</surname><given-names>K.</given-names></name><name><surname>Bartlam</surname><given-names>M.</given-names></name><name><surname>Hilgenfeld</surname><given-names>R.</given-names></name><name><surname>Rao</surname><given-names>Z.</given-names></name></person-group><article-title>The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor</article-title><source>Proc. Natl. Acad. Sci. USA</source><volume>100</volume><year>2003</year><fpage>13190</fpage><lpage>13195</lpage><pub-id pub-id-type="pmid">14585926</pub-id></element-citation></ref><ref id="bib3"><label>3</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Egloff</surname><given-names>M.P.</given-names></name><name><surname>Ferron</surname><given-names>F.</given-names></name><name><surname>Campanacci</surname><given-names>V.</given-names></name><name><surname>Longhi</surname><given-names>S.</given-names></name><name><surname>Rancurel</surname><given-names>C.</given-names></name><name><surname>Dutartre</surname><given-names>H.</given-names></name><name><surname>Snijder</surname><given-names>E.J.</given-names></name><name><surname>Gorbalenya</surname><given-names>A.E.</given-names></name><name><surname>Cambillau</surname><given-names>C.</given-names></name><name><surname>Canard</surname><given-names>B.</given-names></name></person-group><article-title>The severe acute respiratory syndrome-coronavirus replicative protein nsp9 is a single-stranded RNA-binding subunit unique in the RNA virus world</article-title><source>Proc. Natl. Acad. Sci. USA</source><volume>101</volume><year>2004</year><fpage>3792</fpage><lpage>3796</lpage><pub-id pub-id-type="pmid">15007178</pub-id></element-citation></ref><ref id="bib4"><label>4</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shen</surname><given-names>X.</given-names></name><name><surname>Xue</surname><given-names>J.H.</given-names></name><name><surname>Yu</surname><given-names>C.Y.</given-names></name><name><surname>Luo</surname><given-names>H.B.</given-names></name><name><surname>Qin</surname><given-names>L.</given-names></name><name><surname>Yu</surname><given-names>X.J.</given-names></name><name><surname>Chen</surname><given-names>J.</given-names></name><name><surname>Chen</surname><given-names>L.L.</given-names></name><name><surname>Xiong</surname><given-names>B.</given-names></name><name><surname>Yue</surname><given-names>L.D.</given-names></name><name><surname>Cai</surname><given-names>J.H.</given-names></name><name><surname>Shen</surname><given-names>J.H.</given-names></name><name><surname>Luo</surname><given-names>X.M.</given-names></name><name><surname>Chen</surname><given-names>K.X.</given-names></name><name><surname>Shi</surname><given-names>T.L.</given-names></name><name><surname>Li</surname><given-names>Y.X.</given-names></name><name><surname>Hu</surname><given-names>G.X.</given-names></name><name><surname>Jiang</surname><given-names>H.L.</given-names></name></person-group><article-title>Small envelope protein E of SARS: cloning, expression, purification, CD determination, and bioinformatics analysis</article-title><source>Acta Pharmacol. Sin.</source><volume>24</volume><year>2003</year><fpage>505</fpage><lpage>511</lpage><pub-id pub-id-type="pmid">12791175</pub-id></element-citation></ref><ref id="bib5"><label>5</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Spiga</surname><given-names>O.</given-names></name><name><surname>Bernini</surname><given-names>A.</given-names></name><name><surname>Ciutti</surname><given-names>A.</given-names></name><name><surname>Chiellini</surname><given-names>S.</given-names></name><name><surname>Menciassi</surname><given-names>N.</given-names></name><name><surname>Finetti</surname><given-names>F.</given-names></name><name><surname>Causarono</surname><given-names>V.</given-names></name><name><surname>Anselmi</surname><given-names>F.</given-names></name><name><surname>Prischi</surname><given-names>F.</given-names></name><name><surname>Niccolai</surname><given-names>N.</given-names></name></person-group><article-title>Molecular modelling of S1 and S2 subunits of SARS coronavirus spike glycoprotein</article-title><source>Biochem. Biophys. Res. Commun.</source><volume>310</volume><year>2003</year><fpage>78</fpage><lpage>83</lpage><pub-id pub-id-type="pmid">14511651</pub-id></element-citation></ref><ref id="bib6"><label>6</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Xu</surname><given-names>X.</given-names></name><name><surname>Liu</surname><given-names>Y.</given-names></name><name><surname>Weiss</surname><given-names>S.</given-names></name><name><surname>Arnold</surname><given-names>E.</given-names></name><name><surname>Sarafianos</surname><given-names>S.G.</given-names></name><name><surname>Ding</surname><given-names>J.</given-names></name></person-group><article-title>Molecular model of SARS coronavirus polymerase: implications for biochemical functions and drug design</article-title><source>Nucleic Acids Res.</source><volume>31</volume><year>2003</year><fpage>7117</fpage><lpage>7130</lpage><pub-id pub-id-type="pmid">14654687</pub-id></element-citation></ref><ref id="bib7"><label>7</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Cavanagh</surname><given-names>D.</given-names></name></person-group><chapter-title>The Coronavirus Surface Glycoprotein</chapter-title><edition>second ed.</edition><year>1995</year><publisher-name>Plenum Press</publisher-name><publisher-loc>New York</publisher-loc></element-citation></ref><ref id="bib8"><label>8</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lin</surname><given-names>Y.</given-names></name><name><surname>Yan</surname><given-names>X.</given-names></name><name><surname>Cao</surname><given-names>W.</given-names></name><name><surname>Wang</surname><given-names>C.</given-names></name><name><surname>Feng</surname><given-names>J.</given-names></name><name><surname>Duan</surname><given-names>J.</given-names></name><name><surname>Xie</surname><given-names>S.</given-names></name></person-group><article-title>Probing the structure of the SARS coronavirus using scanning electron microscopy</article-title><source>Antivir. Ther.</source><volume>9</volume><year>2004</year><fpage>287</fpage><lpage>289</lpage><pub-id pub-id-type="pmid">15134191</pub-id></element-citation></ref><ref id="bib9"><label>9</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>de Groot</surname><given-names>R.J.</given-names></name><name><surname>Luytjes</surname><given-names>W.</given-names></name><name><surname>Horzinek</surname><given-names>M.C.</given-names></name><name><surname>van der Zeijst</surname><given-names>B.A.</given-names></name><name><surname>Spaan</surname><given-names>W.J.</given-names></name><name><surname>Lenstra</surname><given-names>J.A.</given-names></name></person-group><article-title>Evidence for a coiled-coil structure in the spike proteins of coronaviruses</article-title><source>J. Mol. Biol.</source><volume>196</volume><year>1987</year><fpage>963</fpage><lpage>966</lpage><pub-id pub-id-type="pmid">3681988</pub-id></element-citation></ref><ref id="bib10"><label>10</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Berman</surname><given-names>H.M.</given-names></name><name><surname>Westbrook</surname><given-names>J.</given-names></name><name><surname>Feng</surname><given-names>Z.</given-names></name><name><surname>Gilliland</surname><given-names>G.</given-names></name><name><surname>Bhat</surname><given-names>T.N.</given-names></name><name><surname>Weissig</surname><given-names>H.</given-names></name><name><surname>Shindyalov</surname><given-names>I.N.</given-names></name><name><surname>Bourne</surname><given-names>P.E.</given-names></name></person-group><article-title>The protein data bank</article-title><source>Nucleic Acids Res.</source><volume>28</volume><year>2000</year><fpage>235</fpage><lpage>242</lpage><pub-id pub-id-type="pmid">10592235</pub-id></element-citation></ref><ref id="bib11"><label>11</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sippl</surname><given-names>M.J.</given-names></name></person-group><article-title>Recognition of errors in three-dimensional structures of proteins</article-title><source>Proteins</source><volume>17</volume><year>1993</year><fpage>355</fpage><lpage>362</lpage><pub-id pub-id-type="pmid">8108378</pub-id></element-citation></ref><ref id="bib12"><label>12</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Berendsen</surname><given-names>H.J.C.</given-names></name><name><surname>van der Spoel</surname><given-names>D.</given-names></name><name><surname>van Drunen</surname><given-names>R.</given-names></name></person-group><article-title>GROMACS: a message-passing parallel molecular dynamics implementation</article-title><source>Comp. Phys. Commun.</source><volume>91</volume><year>1995</year><fpage>43</fpage><lpage>56</lpage></element-citation></ref><ref id="bib13"><label>13</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Koradi</surname><given-names>R.</given-names></name><name><surname>Billeter</surname><given-names>M.</given-names></name><name><surname>Wuthrich</surname><given-names>K.</given-names></name></person-group><article-title>MOLMOL: a program for display and analysis of macromolecular structures</article-title><source>J. Mol. Graph.</source><volume>14</volume><year>1996</year><fpage>51</fpage><lpage>55</lpage><comment>29–32</comment><pub-id pub-id-type="pmid">8744573</pub-id></element-citation></ref><ref id="bib14"><label>14</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lewicki</surname><given-names>D.N.</given-names></name><name><surname>Gallagher</surname><given-names>T.M.</given-names></name></person-group><article-title>Quaternary structure of coronavirus spikes in complex with carcinoembryonic antigen-related cell adhesion molecule cellular receptors</article-title><source>J. Biol. Chem.</source><volume>277</volume><year>2002</year><fpage>19727</fpage><lpage>19734</lpage><pub-id pub-id-type="pmid">11912215</pub-id></element-citation></ref><ref id="bib15"><label>15</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wong</surname><given-names>S.K.</given-names></name><name><surname>Li</surname><given-names>W.</given-names></name><name><surname>Moore</surname><given-names>M.J.</given-names></name><name><surname>Choe</surname><given-names>H.</given-names></name><name><surname>Farzan</surname><given-names>M.</given-names></name></person-group><article-title>A 193-amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2</article-title><source>J. Biol. Chem.</source><volume>279</volume><year>2004</year><fpage>3197</fpage><lpage>3201</lpage><pub-id pub-id-type="pmid">14670965</pub-id></element-citation></ref><ref id="bib16"><label>16</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Thompson</surname><given-names>J.D.</given-names></name><name><surname>Higgins</surname><given-names>D.G.</given-names></name><name><surname>Gibson</surname><given-names>T.J.</given-names></name></person-group><article-title>CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice</article-title><source>Nucleic Acids Res.</source><volume>22</volume><year>1994</year><fpage>4673</fpage><lpage>4680</lpage><pub-id pub-id-type="pmid">7984417</pub-id></element-citation></ref><ref id="bib17"><label>17</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sauter</surname><given-names>N.K.</given-names></name><name><surname>Hanson</surname><given-names>J.E.</given-names></name><name><surname>Glick</surname><given-names>G.D.</given-names></name><name><surname>Brown</surname><given-names>J.H.</given-names></name><name><surname>Crowther</surname><given-names>R.L.</given-names></name><name><surname>Park</surname><given-names>S.J.</given-names></name><name><surname>Skehel</surname><given-names>J.J.</given-names></name><name><surname>Wiley</surname><given-names>D.C.</given-names></name></person-group><article-title>Binding of influenza virus hemagglutinin to analogs of its cell-surface receptor, sialic acid: analysis by proton nuclear magnetic resonance spectroscopy and X-ray crystallography</article-title><source>Biochemistry</source><volume>31</volume><year>1992</year><fpage>9609</fpage><lpage>9621</lpage><pub-id pub-id-type="pmid">1327122</pub-id></element-citation></ref><ref id="bib18"><label>18</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Delmas</surname><given-names>B.</given-names></name><name><surname>Laude</surname><given-names>H.</given-names></name></person-group><article-title>Assembly of coronavirus spike protein into trimers and its role in epitope expression</article-title><source>J. Virol.</source><volume>64</volume><year>1990</year><fpage>5367</fpage><lpage>5375</lpage><pub-id pub-id-type="pmid">2170676</pub-id></element-citation></ref><ref id="bib19"><label>19</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wolf</surname><given-names>E.</given-names></name><name><surname>Kim</surname><given-names>P.S.</given-names></name><name><surname>Berger</surname><given-names>B.</given-names></name></person-group><article-title>MultiCoil: a program for predicting two- and three-stranded coiled coils</article-title><source>Protein Sci.</source><volume>6</volume><year>1997</year><fpage>1179</fpage><lpage>1189</lpage><pub-id pub-id-type="pmid">9194178</pub-id></element-citation></ref><ref id="bib20"><label>20</label><mixed-citation publication-type="other">B. Zheng, Y. Guan, L. Du, Y. Zheng, Y. Chen, K.L. Wong, H. Sun, J. Huang, N. Niccolai, A. Bernini, O. Spiga, K.Y. Yuen, H.F. Kung, and M.L. He, Protection of SARS-associated coronavirus infection by peptides targeting the viral spike protein (in preparation)</mixed-citation></ref><ref id="bib21"><label>21</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kyte</surname><given-names>J.</given-names></name><name><surname>Doolittle</surname><given-names>R.F.</given-names></name></person-group><article-title>A simple method for displaying the hydropathic character of a protein</article-title><source>J. Mol. Biol.</source><volume>157</volume><year>1982</year><fpage>105</fpage><lpage>132</lpage><pub-id pub-id-type="pmid">7108955</pub-id></element-citation></ref><ref id="bib22"><label>22</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhu</surname><given-names>J.</given-names></name><name><surname>Xiao</surname><given-names>G.</given-names></name><name><surname>Xu</surname><given-names>Y.</given-names></name><name><surname>Yuan</surname><given-names>F.</given-names></name><name><surname>Zheng</surname><given-names>C.</given-names></name><name><surname>Liu</surname><given-names>Y.</given-names></name><name><surname>Yan</surname><given-names>H.</given-names></name><name><surname>Cole</surname><given-names>D.K.</given-names></name><name><surname>Bell</surname><given-names>J.I.</given-names></name><name><surname>Rao</surname><given-names>Z.</given-names></name><name><surname>Tien</surname><given-names>P.</given-names></name><name><surname>Gao</surname><given-names>G.F.</given-names></name></person-group><article-title>Following the rule: formation of the 6-helix bundle of the fusion core from severe acute respiratory syndrome coronavirus spike protein and identification of potent peptide inhibitors</article-title><source>Biochem. Biophys. Res. Commun.</source><volume>319</volume><year>2004</year><fpage>283</fpage><lpage>288</lpage><pub-id pub-id-type="pmid">15158473</pub-id></element-citation></ref><ref id="bib23"><label>23</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Liu</surname><given-names>S.</given-names></name><name><surname>Xiao</surname><given-names>G.</given-names></name><name><surname>Chen</surname><given-names>Y.</given-names></name><name><surname>He</surname><given-names>Y.</given-names></name><name><surname>Niu</surname><given-names>J.</given-names></name><name><surname>Escalante</surname><given-names>C.R.</given-names></name><name><surname>Xiong</surname><given-names>H.</given-names></name><name><surname>Farmar</surname><given-names>J.</given-names></name><name><surname>Debnath</surname><given-names>A.K.</given-names></name><name><surname>Tien</surname><given-names>P.</given-names></name><name><surname>Jiang</surname><given-names>S.</given-names></name></person-group><article-title>Interaction between heptad repeat 1 and 2 regions in spike protein of SARS-associated coronavirus: implications for virus fusogenic mechanism and identification of fusion inhibitors</article-title><source>Lancet</source><volume>363</volume><year>2004</year><fpage>938</fpage><lpage>947</lpage><pub-id pub-id-type="pmid">15043961</pub-id></element-citation></ref><ref id="bib24"><label>24</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Xu</surname><given-names>Y.</given-names></name><name><surname>Liu</surname><given-names>Y.</given-names></name><name><surname>Lou</surname><given-names>Z.</given-names></name><name><surname>Qin</surname><given-names>L.</given-names></name><name><surname>Li</surname><given-names>X.</given-names></name><name><surname>Bai</surname><given-names>Z.</given-names></name><name><surname>Pang</surname><given-names>H.</given-names></name><name><surname>Tien</surname><given-names>P.</given-names></name><name><surname>Gao</surname><given-names>G.F.</given-names></name><name><surname>Rao</surname><given-names>Z.</given-names></name></person-group><article-title>Structural basis for coronavirus-mediated membrane fusion: crystal structure of MHV spike protein fusion core</article-title><source>J. Biol. Chem.</source><year>2004</year></element-citation></ref></ref-list><ack><title>Acknowledgments</title><p>Thanks are due to the University of Siena for financial support. N.N. also thanks Matteo Bernini for helpful discussions.</p></ack></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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