Crystal Structure of the Full-Length Japanese Encephalitis Virus NS5 Reveals a Conserved Methyltransferase-Polymerase Interface
Identifieur interne : 000396 ( Ncbi/Merge ); précédent : 000395; suivant : 000397Crystal Structure of the Full-Length Japanese Encephalitis Virus NS5 Reveals a Conserved Methyltransferase-Polymerase Interface
Auteurs : Guoliang Lu [République populaire de Chine] ; Peng Gong [République populaire de Chine]Source :
- PLoS Pathogens [ 1553-7366 ] ; 2013.
Abstract
The flavivirus NS5 harbors a methyltransferase (MTase) in its N-terminal ≈265 residues and an RNA-dependent RNA polymerase (RdRP) within the C-terminal part. One of the major interests and challenges in NS5 is to understand the interplay between RdRP and MTase as a unique natural fusion protein in viral genome replication and cap formation. Here, we report the first crystal structure of the full-length flavivirus NS5 from Japanese encephalitis virus. The structure completes the vision for polymerase motifs F and G, and depicts defined intra-molecular interactions between RdRP and MTase. Key hydrophobic residues in the RdRP-MTase interface are highly conserved in flaviviruses, indicating the biological relevance of the observed conformation. Our work paves the way for further dissection of the inter-regulations of the essential enzymatic activities of NS5 and exploration of possible other conformations of NS5 under different circumstances.
Url:
DOI: 10.1371/journal.ppat.1003549
PubMed: 23950717
PubMed Central: 3738499
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PMC:3738499Le document en format XML
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One of the major interests and challenges in NS5 is to understand the interplay between RdRP and MTase as a unique natural fusion protein in viral genome replication and cap formation. Here, we report the first crystal structure of the full-length flavivirus NS5 from Japanese encephalitis virus. The structure completes the vision for polymerase motifs F and G, and depicts defined intra-molecular interactions between RdRP and MTase. Key hydrophobic residues in the RdRP-MTase interface are highly conserved in flaviviruses, indicating the biological relevance of the observed conformation. Our work paves the way for further dissection of the inter-regulations of the essential enzymatic activities of NS5 and exploration of possible other conformations of NS5 under different circumstances.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Cleaves, Gr" uniqKey="Cleaves G">GR Cleaves</name></author><author><name sortKey="Dubin, Dt" uniqKey="Dubin D">DT Dubin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Egloff, Mp" uniqKey="Egloff M">MP Egloff</name></author><author><name sortKey="Benarroch, D" uniqKey="Benarroch D">D Benarroch</name></author><author><name sortKey="Selisko, B" uniqKey="Selisko B">B Selisko</name></author><author><name sortKey="Romette, Jl" uniqKey="Romette J">JL Romette</name></author><author><name sortKey="Canard, B" uniqKey="Canard B">B Canard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, L" uniqKey="Liu L">L Liu</name></author><author><name sortKey="Dong, H" uniqKey="Dong H">H Dong</name></author><author><name sortKey="Chen, H" uniqKey="Chen H">H Chen</name></author><author><name sortKey="Zhang, J" uniqKey="Zhang J">J Zhang</name></author><author><name sortKey="Ling, H" uniqKey="Ling H">H Ling</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Geiss, Bj" uniqKey="Geiss B">BJ Geiss</name></author><author><name sortKey="Thompson, Aa" uniqKey="Thompson A">AA Thompson</name></author><author><name sortKey="Andrews, Aj" uniqKey="Andrews A">AJ Andrews</name></author><author><name sortKey="Sons, Rl" uniqKey="Sons R">RL Sons</name></author><author><name sortKey="Gari, Hh" uniqKey="Gari H">HH Gari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ray, D" uniqKey="Ray D">D Ray</name></author><author><name sortKey="Shah, A" uniqKey="Shah A">A Shah</name></author><author><name sortKey="Tilgner, M" uniqKey="Tilgner M">M Tilgner</name></author><author><name sortKey="Guo, Y" uniqKey="Guo Y">Y Guo</name></author><author><name sortKey="Zhao, Y" uniqKey="Zhao Y">Y Zhao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Issur, M" uniqKey="Issur M">M Issur</name></author><author><name sortKey="Geiss, Bj" uniqKey="Geiss B">BJ Geiss</name></author><author><name sortKey="Bougie, I" uniqKey="Bougie I">I Bougie</name></author><author><name sortKey="Picard Jean, F" uniqKey="Picard Jean F">F Picard-Jean</name></author><author><name sortKey="Despins, S" uniqKey="Despins S">S Despins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Malet, H" uniqKey="Malet H">H Malet</name></author><author><name sortKey="Egloff, Mp" uniqKey="Egloff M">MP Egloff</name></author><author><name sortKey="Selisko, B" uniqKey="Selisko B">B Selisko</name></author><author><name sortKey="Butcher, Re" uniqKey="Butcher R">RE Butcher</name></author><author><name sortKey="Wright, Pj" uniqKey="Wright P">PJ Wright</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yap, Tl" uniqKey="Yap T">TL Yap</name></author><author><name sortKey="Xu, T" uniqKey="Xu T">T Xu</name></author><author><name sortKey="Chen, Yl" uniqKey="Chen Y">YL Chen</name></author><author><name sortKey="Malet, H" uniqKey="Malet H">H Malet</name></author><author><name sortKey="Egloff, Mp" uniqKey="Egloff M">MP Egloff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lesburg, Ca" uniqKey="Lesburg C">CA Lesburg</name></author><author><name sortKey="Cable, Mb" uniqKey="Cable M">MB Cable</name></author><author><name sortKey="Ferrari, E" uniqKey="Ferrari E">E Ferrari</name></author><author><name sortKey="Hong, Z" uniqKey="Hong Z">Z Hong</name></author><author><name sortKey="Mannarino, Af" uniqKey="Mannarino A">AF Mannarino</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Choi, Kh" uniqKey="Choi K">KH Choi</name></author><author><name sortKey="Groarke, Jm" uniqKey="Groarke J">JM Groarke</name></author><author><name sortKey="Young, Dc" uniqKey="Young D">DC Young</name></author><author><name sortKey="Kuhn, Rj" uniqKey="Kuhn R">RJ Kuhn</name></author><author><name sortKey="Smith, Jl" uniqKey="Smith J">JL Smith</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thompson, Aa" uniqKey="Thompson A">AA Thompson</name></author><author><name sortKey="Peersen, Ob" uniqKey="Peersen O">OB Peersen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gong, P" uniqKey="Gong P">P Gong</name></author><author><name sortKey="Peersen, Ob" uniqKey="Peersen O">OB Peersen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, B" uniqKey="Zhang B">B Zhang</name></author><author><name sortKey="Dong, H" uniqKey="Dong H">H Dong</name></author><author><name sortKey="Zhou, Y" uniqKey="Zhou Y">Y Zhou</name></author><author><name sortKey="Shi, Py" uniqKey="Shi P">PY Shi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Filomatori, Cv" uniqKey="Filomatori C">CV Filomatori</name></author><author><name sortKey="Lodeiro, Mf" uniqKey="Lodeiro M">MF Lodeiro</name></author><author><name sortKey="Alvarez, De" uniqKey="Alvarez D">DE Alvarez</name></author><author><name sortKey="Samsa, Mm" uniqKey="Samsa M">MM Samsa</name></author><author><name sortKey="Pietrasanta, L" uniqKey="Pietrasanta L">L Pietrasanta</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rawlinson, Sm" uniqKey="Rawlinson S">SM Rawlinson</name></author><author><name sortKey="Pryor, Mj" uniqKey="Pryor M">MJ Pryor</name></author><author><name sortKey="Wright, Pj" uniqKey="Wright P">PJ Wright</name></author><author><name sortKey="Jans, Da" uniqKey="Jans D">DA Jans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brooks, Aj" uniqKey="Brooks A">AJ Brooks</name></author><author><name sortKey="Johansson, M" uniqKey="Johansson M">M Johansson</name></author><author><name sortKey="John, Av" uniqKey="John A">AV John</name></author><author><name sortKey="Xu, Y" uniqKey="Xu Y">Y Xu</name></author><author><name sortKey="Jans, Da" uniqKey="Jans D">DA Jans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vasudevan, Sg" uniqKey="Vasudevan S">SG Vasudevan</name></author><author><name sortKey="Johansson, M" uniqKey="Johansson M">M Johansson</name></author><author><name sortKey="Brooks, Aj" uniqKey="Brooks A">AJ Brooks</name></author><author><name sortKey="Llewellyn, Le" uniqKey="Llewellyn L">LE Llewellyn</name></author><author><name sortKey="Jans, Da" uniqKey="Jans D">DA Jans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Forwood, Jk" uniqKey="Forwood J">JK Forwood</name></author><author><name sortKey="Brooks, A" uniqKey="Brooks A">A Brooks</name></author><author><name sortKey="Briggs, Lj" uniqKey="Briggs L">LJ Briggs</name></author><author><name sortKey="Xiao, Cy" uniqKey="Xiao C">CY Xiao</name></author><author><name sortKey="Jans, Da" uniqKey="Jans D">DA Jans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bussetta, C" uniqKey="Bussetta C">C Bussetta</name></author><author><name sortKey="Choi, Kh" uniqKey="Choi K">KH Choi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Assenberg, R" uniqKey="Assenberg R">R Assenberg</name></author><author><name sortKey="Ren, J" uniqKey="Ren J">J Ren</name></author><author><name sortKey="Verma, A" uniqKey="Verma A">A Verma</name></author><author><name sortKey="Walter, Ts" uniqKey="Walter T">TS Walter</name></author><author><name sortKey="Alderton, D" uniqKey="Alderton D">D Alderton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Butcher, Sj" uniqKey="Butcher S">SJ Butcher</name></author><author><name sortKey="Grimes, Jm" uniqKey="Grimes J">JM Grimes</name></author><author><name sortKey="Makeyev, Ev" uniqKey="Makeyev E">EV Makeyev</name></author><author><name sortKey="Bamford, Dh" uniqKey="Bamford D">DH Bamford</name></author><author><name sortKey="Stuart, Di" uniqKey="Stuart D">DI Stuart</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Johansson, M" uniqKey="Johansson M">M Johansson</name></author><author><name sortKey="Brooks, Aj" uniqKey="Brooks A">AJ Brooks</name></author><author><name sortKey="Jans, Da" uniqKey="Jans D">DA Jans</name></author><author><name sortKey="Vasudevan, Sg" uniqKey="Vasudevan S">SG Vasudevan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pryor, Mj" uniqKey="Pryor M">MJ Pryor</name></author><author><name sortKey="Rawlinson, Sm" uniqKey="Rawlinson S">SM Rawlinson</name></author><author><name sortKey="Butcher, Re" uniqKey="Butcher R">RE Butcher</name></author><author><name sortKey="Barton, Cl" uniqKey="Barton C">CL Barton</name></author><author><name sortKey="Waterhouse, Ta" uniqKey="Waterhouse T">TA Waterhouse</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, Y" uniqKey="Wu Y">Y Wu</name></author><author><name sortKey="Lou, Z" uniqKey="Lou Z">Z Lou</name></author><author><name sortKey="Miao, Y" uniqKey="Miao Y">Y Miao</name></author><author><name sortKey="Yu, Y" uniqKey="Yu Y">Y Yu</name></author><author><name sortKey="Dong, H" uniqKey="Dong H">H Dong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zamyatkin, Df" uniqKey="Zamyatkin D">DF Zamyatkin</name></author><author><name sortKey="Parra, F" uniqKey="Parra F">F Parra</name></author><author><name sortKey="Alonso, Jm" uniqKey="Alonso J">JM Alonso</name></author><author><name sortKey="Harki, Da" uniqKey="Harki D">DA Harki</name></author><author><name sortKey="Peterson, Br" uniqKey="Peterson B">BR Peterson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jager, J" uniqKey="Jager J">J Jager</name></author><author><name sortKey="Smerdon, Sj" uniqKey="Smerdon S">SJ Smerdon</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J Wang</name></author><author><name sortKey="Boisvert, Dc" uniqKey="Boisvert D">DC Boisvert</name></author><author><name sortKey="Steitz, Ta" uniqKey="Steitz T">TA Steitz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Choi, Kh" uniqKey="Choi K">KH Choi</name></author><author><name sortKey="Gallei, A" uniqKey="Gallei A">A Gallei</name></author><author><name sortKey="Becher, P" uniqKey="Becher P">P Becher</name></author><author><name sortKey="Rossmann, Mg" uniqKey="Rossmann M">MG Rossmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brocchieri, L" uniqKey="Brocchieri L">L Brocchieri</name></author><author><name sortKey="Karlin, S" uniqKey="Karlin S">S Karlin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, Y" uniqKey="Zhou Y">Y Zhou</name></author><author><name sortKey="Ray, D" uniqKey="Ray D">D Ray</name></author><author><name sortKey="Zhao, Y" uniqKey="Zhao Y">Y Zhao</name></author><author><name sortKey="Dong, H" uniqKey="Dong H">H Dong</name></author><author><name sortKey="Ren, S" uniqKey="Ren S">S Ren</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bressanelli, S" uniqKey="Bressanelli S">S Bressanelli</name></author><author><name sortKey="Tomei, L" uniqKey="Tomei L">L Tomei</name></author><author><name sortKey="Roussel, A" uniqKey="Roussel A">A Roussel</name></author><author><name sortKey="Incitti, I" uniqKey="Incitti I">I Incitti</name></author><author><name sortKey="Vitale, Rl" uniqKey="Vitale R">RL Vitale</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marcotte, Ll" uniqKey="Marcotte L">LL Marcotte</name></author><author><name sortKey="Wass, Ab" uniqKey="Wass A">AB Wass</name></author><author><name sortKey="Gohara, Dw" uniqKey="Gohara D">DW Gohara</name></author><author><name sortKey="Pathak, Hb" uniqKey="Pathak H">HB Pathak</name></author><author><name sortKey="Arnold, Jj" uniqKey="Arnold J">JJ Arnold</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y Chen</name></author><author><name sortKey="Su, C" uniqKey="Su C">C Su</name></author><author><name sortKey="Ke, M" uniqKey="Ke M">M Ke</name></author><author><name sortKey="Jin, X" uniqKey="Jin X">X Jin</name></author><author><name sortKey="Xu, L" uniqKey="Xu L">L Xu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mastrangelo, E" uniqKey="Mastrangelo E">E Mastrangelo</name></author><author><name sortKey="Bollati, M" uniqKey="Bollati M">M Bollati</name></author><author><name sortKey="Milani, M" uniqKey="Milani M">M Milani</name></author><author><name sortKey="Selisko, B" uniqKey="Selisko B">B Selisko</name></author><author><name sortKey="Peyrane, F" uniqKey="Peyrane F">F Peyrane</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bollati, M" uniqKey="Bollati M">M Bollati</name></author><author><name sortKey="Milani, M" uniqKey="Milani M">M Milani</name></author><author><name sortKey="Mastrangelo, E" uniqKey="Mastrangelo E">E Mastrangelo</name></author><author><name sortKey="Ricagno, S" uniqKey="Ricagno S">S Ricagno</name></author><author><name sortKey="Tedeschi, G" uniqKey="Tedeschi G">G Tedeschi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q Wang</name></author><author><name sortKey="Weng, L" uniqKey="Weng L">L Weng</name></author><author><name sortKey="Tian, X" uniqKey="Tian X">X Tian</name></author><author><name sortKey="Counor, D" uniqKey="Counor D">D Counor</name></author><author><name sortKey="Sun, J" uniqKey="Sun J">J Sun</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gong, P" uniqKey="Gong P">P Gong</name></author><author><name sortKey="Kortus, Mg" uniqKey="Kortus M">MG Kortus</name></author><author><name sortKey="Nix, Jc" uniqKey="Nix J">JC Nix</name></author><author><name sortKey="Davis, Re" uniqKey="Davis R">RE Davis</name></author><author><name sortKey="Peersen, Ob" uniqKey="Peersen O">OB Peersen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Martin, Ct" uniqKey="Martin C">CT Martin</name></author><author><name sortKey="Muller, Dk" uniqKey="Muller D">DK Muller</name></author><author><name sortKey="Coleman, Je" uniqKey="Coleman J">JE Coleman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carpousis, Aj" uniqKey="Carpousis A">AJ Carpousis</name></author><author><name sortKey="Gralla, Jd" uniqKey="Gralla J">JD Gralla</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kao, Cc" uniqKey="Kao C">CC Kao</name></author><author><name sortKey="Yang, X" uniqKey="Yang X">X Yang</name></author><author><name sortKey="Kline, A" uniqKey="Kline A">A Kline</name></author><author><name sortKey="Wang, Qm" uniqKey="Wang Q">QM Wang</name></author><author><name sortKey="Barket, D" uniqKey="Barket D">D Barket</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Selisko, B" uniqKey="Selisko B">B Selisko</name></author><author><name sortKey="Dutartre, H" uniqKey="Dutartre H">H Dutartre</name></author><author><name sortKey="Guillemot, Jc" uniqKey="Guillemot J">JC Guillemot</name></author><author><name sortKey="Debarnot, C" uniqKey="Debarnot C">C Debarnot</name></author><author><name sortKey="Benarroch, D" uniqKey="Benarroch D">D Benarroch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gong, P" uniqKey="Gong P">P Gong</name></author><author><name sortKey="Martin, Ct" uniqKey="Martin C">CT Martin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mosley, Rt" uniqKey="Mosley R">RT Mosley</name></author><author><name sortKey="Edwards, Te" uniqKey="Edwards T">TE Edwards</name></author><author><name sortKey="Murakami, E" uniqKey="Murakami E">E Murakami</name></author><author><name sortKey="Lam, Am" uniqKey="Lam A">AM Lam</name></author><author><name sortKey="Grice, Rl" uniqKey="Grice R">RL Grice</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jin, Z" uniqKey="Jin Z">Z Jin</name></author><author><name sortKey="Leveque, V" uniqKey="Leveque V">V Leveque</name></author><author><name sortKey="Ma, H" uniqKey="Ma H">H Ma</name></author><author><name sortKey="Johnson, Ka" uniqKey="Johnson K">KA Johnson</name></author><author><name sortKey="Klumpp, K" uniqKey="Klumpp K">K Klumpp</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gohara, Dw" uniqKey="Gohara D">DW Gohara</name></author><author><name sortKey="Ha, Cs" uniqKey="Ha C">CS Ha</name></author><author><name sortKey="Kumar, S" uniqKey="Kumar S">S Kumar</name></author><author><name sortKey="Ghosh, B" uniqKey="Ghosh B">B Ghosh</name></author><author><name sortKey="Arnold, Jj" uniqKey="Arnold J">JJ Arnold</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pflugrath, Jw" uniqKey="Pflugrath J">JW Pflugrath</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mccoy, Aj" uniqKey="Mccoy A">AJ McCoy</name></author><author><name sortKey="Grosse Kunstleve, Rw" uniqKey="Grosse Kunstleve R">RW Grosse-Kunstleve</name></author><author><name sortKey="Adams, Pd" uniqKey="Adams P">PD Adams</name></author><author><name sortKey="Winn, Md" uniqKey="Winn M">MD Winn</name></author><author><name sortKey="Storoni, Lc" uniqKey="Storoni L">LC Storoni</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Emsley, P" uniqKey="Emsley P">P Emsley</name></author><author><name sortKey="Cowtan, K" uniqKey="Cowtan K">K Cowtan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Adams, Pd" uniqKey="Adams P">PD Adams</name></author><author><name sortKey="Grosse Kunstleve, Rw" uniqKey="Grosse Kunstleve R">RW Grosse-Kunstleve</name></author><author><name sortKey="Hung, Lw" uniqKey="Hung L">LW Hung</name></author><author><name sortKey="Ioerger, Tr" uniqKey="Ioerger T">TR Ioerger</name></author><author><name sortKey="Mccoy, Aj" uniqKey="Mccoy A">AJ McCoy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brunger, At" uniqKey="Brunger A">AT Brunger</name></author><author><name sortKey="Adams, Pd" uniqKey="Adams P">PD Adams</name></author><author><name sortKey="Clore, Gm" uniqKey="Clore G">GM Clore</name></author><author><name sortKey="Delano, Wl" uniqKey="Delano W">WL DeLano</name></author><author><name sortKey="Gros, P" uniqKey="Gros P">P Gros</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">PLoS Pathog</journal-id><journal-id journal-id-type="iso-abbrev">PLoS Pathog</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plospath</journal-id><journal-title-group><journal-title>PLoS Pathogens</journal-title></journal-title-group><issn pub-type="ppub">1553-7366</issn><issn pub-type="epub">1553-7374</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23950717</article-id><article-id pub-id-type="pmc">3738499</article-id><article-id pub-id-type="publisher-id">PPATHOGENS-D-13-01277</article-id><article-id pub-id-type="doi">10.1371/journal.ppat.1003549</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biology</subject><subj-group><subject>Biochemistry</subject><subj-group><subject>Proteins</subject><subj-group><subject>Protein Structure</subject></subj-group></subj-group></subj-group><subj-group><subject>Microbiology</subject><subj-group><subject>Virology</subject><subj-group><subject>Viral Enzymes</subject><subject>Viral Replication</subject></subj-group></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Crystal Structure of the Full-Length Japanese Encephalitis Virus NS5 Reveals a Conserved Methyltransferase-Polymerase Interface</article-title><alt-title alt-title-type="running-head">Crystal Structure of the Full-Length JEV NS5</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Lu</surname><given-names>Guoliang</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gong</surname><given-names>Peng</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuchang District, Wuhan, Hubei, China</addr-line></aff><aff id="aff2"><label>2</label><addr-line>University of Chinese Academy of Sciences, Beijing, China</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Tellinghuisen</surname><given-names>Timothy L.</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>The Scripps Research Institute, United States of America</addr-line></aff><author-notes><corresp id="cor1">* E-mail: <email>GongPeng2001@yahoo.com</email>, <email>GongPeng@wh.iov.cn</email></corresp><fn fn-type="COI-statement"><p>The authors have declared that no competing interests exist.</p></fn><fn fn-type="con"><p>Conceived and designed the experiments: PG. Performed the experiments: GL PG. Analyzed the data: PG GL. Wrote the paper: PG.</p></fn></author-notes><pub-date pub-type="collection"><month>8</month><year>2013</year></pub-date><pub-date pub-type="epub"><day>8</day><month>8</month><year>2013</year></pub-date><volume>9</volume><issue>8</issue><elocation-id>e1003549</elocation-id><history><date date-type="received"><day>14</day><month>5</month><year>2013</year></date><date date-type="accepted"><day>27</day><month>6</month><year>2013</year></date></history><permissions><copyright-statement>© 2013 Lu and Gong</copyright-statement><copyright-year>2013</copyright-year><copyright-holder>Lu and Gong</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.</license-p></license></permissions><abstract><p>The flavivirus NS5 harbors a methyltransferase (MTase) in its N-terminal ≈265 residues and an RNA-dependent RNA polymerase (RdRP) within the C-terminal part. One of the major interests and challenges in NS5 is to understand the interplay between RdRP and MTase as a unique natural fusion protein in viral genome replication and cap formation. Here, we report the first crystal structure of the full-length flavivirus NS5 from Japanese encephalitis virus. The structure completes the vision for polymerase motifs F and G, and depicts defined intra-molecular interactions between RdRP and MTase. Key hydrophobic residues in the RdRP-MTase interface are highly conserved in flaviviruses, indicating the biological relevance of the observed conformation. Our work paves the way for further dissection of the inter-regulations of the essential enzymatic activities of NS5 and exploration of possible other conformations of NS5 under different circumstances.</p></abstract><abstract abstract-type="summary"><title>Author Summary</title><p>Due to limited coding capacity, RNA viruses often generate proteins that contain more than one enzyme module to fulfill their rather complicated life cycle. Among those, the flavivirus nonstructural protein NS5 comprises an N-terminal methyltransferase (MTase) and a C-terminal RNA-dependent RNA polymerase (RdRP), playing key roles in processes including viral genome replication and capping. Although high-resolution crystal structures are available for MTase or RdRP alone, the intra-molecular interactions between the two modules remain elusive. By solving the crystal-structure of the full-length Japanese encephalitis virus NS5, we provide the first high-resolution readout of NS5 in its integrity, featuring an MTase-RdRP interface that is highly conserved in flaviviruses. Flaviviruses also include other important human pathogens such as dengue, West Nile, yellow fever, and tick-borne encephalitis viruses, currently lacking effective anti-viral drug. The conserved interface revealed by our structure thus may provide possibilities for the pharmaceutical community in the development of anti-flavivirus drug in a broad-spectrum manner.</p></abstract><funding-group><funding-statement>This work was supported in part by the National Key Basic Research Program of China (2013CB9111), and the “Hundred Talents Program” of Chinese Academy of Sciences, China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><page-count count="10"></page-count></counts></article-meta></front></pmc><affiliations><list><country><li>République populaire de Chine</li></country><settlement><li>Pékin</li></settlement></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Lu, Guoliang" sort="Lu, Guoliang" uniqKey="Lu G" first="Guoliang" last="Lu">Guoliang Lu</name></noRegion><name sortKey="Gong, Peng" sort="Gong, Peng" uniqKey="Gong P" first="Peng" last="Gong">Peng Gong</name><name sortKey="Lu, Guoliang" sort="Lu, Guoliang" uniqKey="Lu G" first="Guoliang" last="Lu">Guoliang Lu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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