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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Insights into Avian Influenza Virus Pathogenicity: the Hemagglutinin Precursor HA0 of Subtype H16 Has an Alpha-Helix Structure in Its Cleavage Site with Inefficient HA1/HA2 Cleavage</title><author><name sortKey="Lu, Xishan" sort="Lu, Xishan" uniqKey="Lu X" first="Xishan" last="Lu">Xishan Lu</name><affiliation><nlm:aff id="aff1">College of Veterinary Medicine, China Agricultural University, Beijing, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Shi, Yi" sort="Shi, Yi" uniqKey="Shi Y" first="Yi" last="Shi">Yi Shi</name><affiliation><nlm:aff id="aff2">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Gao, Feng" sort="Gao, Feng" uniqKey="Gao F" first="Feng" last="Gao">Feng Gao</name><affiliation><nlm:aff id="aff3">National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Xiao, Haixia" sort="Xiao, Haixia" uniqKey="Xiao H" first="Haixia" last="Xiao">Haixia Xiao</name><affiliation><nlm:aff id="aff4">Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China</nlm:aff></affiliation></author><author><name sortKey="Wang, Ming" sort="Wang, Ming" uniqKey="Wang M" first="Ming" last="Wang">Ming Wang</name><affiliation><nlm:aff id="aff1">College of Veterinary Medicine, China Agricultural University, Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Qi, Jianxun" sort="Qi, Jianxun" uniqKey="Qi J" first="Jianxun" last="Qi">Jianxun Qi</name><affiliation><nlm:aff id="aff2">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name><affiliation><nlm:aff id="aff1">College of Veterinary Medicine, China Agricultural University, Beijing, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22993148</idno><idno type="pmc">3497694</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3497694</idno><idno type="RBID">PMC:3497694</idno><idno type="doi">10.1128/JVI.01606-12</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000656</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000656</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Insights into Avian Influenza Virus Pathogenicity: the Hemagglutinin Precursor HA0 of Subtype H16 Has an Alpha-Helix Structure in Its Cleavage Site with Inefficient HA1/HA2 Cleavage</title><author><name sortKey="Lu, Xishan" sort="Lu, Xishan" uniqKey="Lu X" first="Xishan" last="Lu">Xishan Lu</name><affiliation><nlm:aff id="aff1">College of Veterinary Medicine, China Agricultural University, Beijing, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Shi, Yi" sort="Shi, Yi" uniqKey="Shi Y" first="Yi" last="Shi">Yi Shi</name><affiliation><nlm:aff id="aff2">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Gao, Feng" sort="Gao, Feng" uniqKey="Gao F" first="Feng" last="Gao">Feng Gao</name><affiliation><nlm:aff id="aff3">National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Xiao, Haixia" sort="Xiao, Haixia" uniqKey="Xiao H" first="Haixia" last="Xiao">Haixia Xiao</name><affiliation><nlm:aff id="aff4">Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China</nlm:aff></affiliation></author><author><name sortKey="Wang, Ming" sort="Wang, Ming" uniqKey="Wang M" first="Ming" last="Wang">Ming Wang</name><affiliation><nlm:aff id="aff1">College of Veterinary Medicine, China Agricultural University, Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Qi, Jianxun" sort="Qi, Jianxun" uniqKey="Qi J" first="Jianxun" last="Qi">Jianxun Qi</name><affiliation><nlm:aff id="aff2">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name><affiliation><nlm:aff id="aff1">College of Veterinary Medicine, China Agricultural University, Beijing, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China</nlm:aff></affiliation></author></analytic><series><title level="j">Journal of Virology</title><idno type="ISSN">0022-538X</idno><idno type="eISSN">1098-5514</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>With a new serotype (H17) of hemagglutinin (HA) recently being discovered, there are now 17 serotypes (H1 to H17) of influenza A viruses in total. It is believed that HA is initially expressed as a precursor of HA0 and then cleaved into HA1 and HA2, forming a disulfide bond-linked complex, for its full function. Structural data show that a loop structure exists in the cleavage site between HA1 and HA2, and this flexible loop is crucial for the efficient cleavage of HA0. Here, the crystal structures of H16 (a low-pathogenicity avian influenza virus) in their HA0 form (H16HA0) have been solved at 1.7-Å and 2.0-Å resolutions. To our surprise, an α-helix element in the cleavage site which inserts into the negatively charged cavity with the key residue R329 hidden behind the helix was observed. <italic>In vitro</italic> trypsin cleavage experiments demonstrated inefficient cleavage of H16HA0 under both neutral and low-pH conditions. The results provide new insights into influenza A virus pathogenicity; both the relatively stable α-helix structure in the flexible cleavage loop and inaccessibility of the cleavage site likely contribute to the low pathogenicity of avian influenza A virus. Furthermore, compared to all of the HAs whose structures have been solved, H16 is a good reference for assigning the HA subtypes into two groups on the basis of the three-dimensional structure, which is consistent with the phylogenetic grouping. We conclude that in light of the current H16HA0 structure, the natural α-helix element might provide a new opportunity for influenza virus inhibitor design.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Virol</journal-id><journal-id journal-id-type="iso-abbrev">J. Virol</journal-id><journal-id journal-id-type="hwp">jvi</journal-id><journal-id journal-id-type="pmc">jvi</journal-id><journal-id journal-id-type="publisher-id">JVI</journal-id><journal-title-group><journal-title>Journal of Virology</journal-title></journal-title-group><issn pub-type="ppub">0022-538X</issn><issn pub-type="epub">1098-5514</issn><publisher><publisher-name>American Society for Microbiology</publisher-name><publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">22993148</article-id><article-id pub-id-type="pmc">3497694</article-id><article-id pub-id-type="publisher-id">01606-12</article-id><article-id pub-id-type="doi">10.1128/JVI.01606-12</article-id><article-categories><subj-group subj-group-type="heading"><subject>Structure and Assembly</subject></subj-group></article-categories><title-group><article-title>Insights into Avian Influenza Virus Pathogenicity: the Hemagglutinin Precursor HA0 of Subtype H16 Has an Alpha-Helix Structure in Its Cleavage Site with Inefficient HA1/HA2 Cleavage</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Lu</surname><given-names>Xishan</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Shi</surname><given-names>Yi</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gao</surname><given-names>Feng</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Xiao</surname><given-names>Haixia</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Ming</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Qi</surname><given-names>Jianxun</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Gao</surname><given-names>George F.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff2"><sup>b</sup></xref><xref ref-type="aff" rid="aff4"><sup>d</sup></xref><xref ref-type="aff" rid="aff5"><sup>e</sup></xref></contrib><aff id="aff1"><label>a</label>College of Veterinary Medicine, China Agricultural University, Beijing, China</aff><aff id="aff2"><label>b</label>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</aff><aff id="aff3"><label>c</label>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China</aff><aff id="aff4"><label>d</label>Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China</aff><aff id="aff5"><label>e</label>Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China</aff></contrib-group><author-notes><corresp>Address correspondence to George F. Gao, <email>gaof@im.ac.cn</email>.</corresp><fn fn-type="equal"><p>X.L., Y.S., and F.G. contributed equally to this article.</p></fn></author-notes><pub-date pub-type="ppub"><month>12</month><year>2012</year></pub-date><volume>86</volume><issue>23</issue><fpage>12861</fpage><lpage>12870</lpage><history><date date-type="received"><day>25</day><month>6</month><year>2012</year></date><date date-type="accepted"><day>10</day><month>9</month><year>2012</year></date></history><permissions><copyright-statement>Copyright © 2012, American Society for Microbiology. All Rights Reserved.</copyright-statement><copyright-year>2012</copyright-year><copyright-holder>American Society for Microbiology</copyright-holder></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zjv02312012861.pdf"></self-uri><abstract><p>With a new serotype (H17) of hemagglutinin (HA) recently being discovered, there are now 17 serotypes (H1 to H17) of influenza A viruses in total. It is believed that HA is initially expressed as a precursor of HA0 and then cleaved into HA1 and HA2, forming a disulfide bond-linked complex, for its full function. Structural data show that a loop structure exists in the cleavage site between HA1 and HA2, and this flexible loop is crucial for the efficient cleavage of HA0. Here, the crystal structures of H16 (a low-pathogenicity avian influenza virus) in their HA0 form (H16HA0) have been solved at 1.7-Å and 2.0-Å resolutions. To our surprise, an α-helix element in the cleavage site which inserts into the negatively charged cavity with the key residue R329 hidden behind the helix was observed. <italic>In vitro</italic> trypsin cleavage experiments demonstrated inefficient cleavage of H16HA0 under both neutral and low-pH conditions. The results provide new insights into influenza A virus pathogenicity; both the relatively stable α-helix structure in the flexible cleavage loop and inaccessibility of the cleavage site likely contribute to the low pathogenicity of avian influenza A virus. Furthermore, compared to all of the HAs whose structures have been solved, H16 is a good reference for assigning the HA subtypes into two groups on the basis of the three-dimensional structure, which is consistent with the phylogenetic grouping. We conclude that in light of the current H16HA0 structure, the natural α-helix element might provide a new opportunity for influenza virus inhibitor design.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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