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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Structure and receptor binding of the hemagglutinin from a human H6N1 influenza virus</title>
<author><name sortKey="Tzarum, Netanel" sort="Tzarum, Netanel" uniqKey="Tzarum N" first="Netanel" last="Tzarum">Netanel Tzarum</name>
<affiliation><nlm:aff id="A1">Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="De Vries, Robert P" sort="De Vries, Robert P" uniqKey="De Vries R" first="Robert P." last="De Vries">Robert P. De Vries</name>
<affiliation><nlm:aff id="A2">Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A4">Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zhu, Xueyong" sort="Zhu, Xueyong" uniqKey="Zhu X" first="Xueyong" last="Zhu">Xueyong Zhu</name>
<affiliation><nlm:aff id="A1">Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Yu, Wenli" sort="Yu, Wenli" uniqKey="Yu W" first="Wenli" last="Yu">Wenli Yu</name>
<affiliation><nlm:aff id="A1">Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mcbride, Ryan" sort="Mcbride, Ryan" uniqKey="Mcbride R" first="Ryan" last="Mcbride">Ryan Mcbride</name>
<affiliation><nlm:aff id="A2">Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A4">Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Paulson, James C" sort="Paulson, James C" uniqKey="Paulson J" first="James C." last="Paulson">James C. Paulson</name>
<affiliation><nlm:aff id="A2">Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A4">Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wilson, Ian A" sort="Wilson, Ian A" uniqKey="Wilson I" first="Ian A." last="Wilson">Ian A. Wilson</name>
<affiliation><nlm:aff id="A1">Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A5">Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">25766295</idno>
<idno type="pmc">4374348</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374348</idno>
<idno type="RBID">PMC:4374348</idno>
<idno type="doi">10.1016/j.chom.2015.02.005</idno>
<date when="2015">2015</date>
<idno type="wicri:Area/Pmc/Corpus">000820</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000820</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Structure and receptor binding of the hemagglutinin from a human H6N1 influenza virus</title>
<author><name sortKey="Tzarum, Netanel" sort="Tzarum, Netanel" uniqKey="Tzarum N" first="Netanel" last="Tzarum">Netanel Tzarum</name>
<affiliation><nlm:aff id="A1">Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="De Vries, Robert P" sort="De Vries, Robert P" uniqKey="De Vries R" first="Robert P." last="De Vries">Robert P. De Vries</name>
<affiliation><nlm:aff id="A2">Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A4">Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zhu, Xueyong" sort="Zhu, Xueyong" uniqKey="Zhu X" first="Xueyong" last="Zhu">Xueyong Zhu</name>
<affiliation><nlm:aff id="A1">Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Yu, Wenli" sort="Yu, Wenli" uniqKey="Yu W" first="Wenli" last="Yu">Wenli Yu</name>
<affiliation><nlm:aff id="A1">Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mcbride, Ryan" sort="Mcbride, Ryan" uniqKey="Mcbride R" first="Ryan" last="Mcbride">Ryan Mcbride</name>
<affiliation><nlm:aff id="A2">Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A4">Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Paulson, James C" sort="Paulson, James C" uniqKey="Paulson J" first="James C." last="Paulson">James C. Paulson</name>
<affiliation><nlm:aff id="A2">Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A4">Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wilson, Ian A" sort="Wilson, Ian A" uniqKey="Wilson I" first="Ian A." last="Wilson">Ian A. Wilson</name>
<affiliation><nlm:aff id="A1">Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A5">Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Cell host & microbe</title>
<idno type="ISSN">1931-3128</idno>
<idno type="eISSN">1934-6069</idno>
<imprint><date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><title>SUMMARY</title>
<p id="P1">Avian influenza viruses that cause infection and are transmissible in humans involve changes in the receptor binding site (RBS) of the viral hemagglutinin (HA) that alter receptor preference from α2-3-linked (avian-like) to α2-6-linked (human-like) sialosides. A human case of avian-origin H6N1 influenza virus was recently reported, but the molecular mechanisms contributing to it crossing the species barrier are unknown. We find that, although the H6 HA RBS contains D190V and G228S substitutions that potentially promote human receptor binding, recombinant H6 HA preferentially binds α2-3-linked sialosides, indicating no adaptation to human receptors. Crystal structures of H6 HA with avian and human receptor analogs reveal that H6 HA preferentially interacts with avian receptor analogs. This binding mechanism differs from other HA subtypes due to a unique combination of RBS residues, highlighting additional variation in HA-receptor interactions and the challenges in predicting which influenza strains and subtypes can infect humans and cause pandemics.</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>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101302316</journal-id>
<journal-id journal-id-type="pubmed-jr-id">33345</journal-id>
<journal-id journal-id-type="nlm-ta">Cell Host Microbe</journal-id>
<journal-id journal-id-type="iso-abbrev">Cell Host Microbe</journal-id>
<journal-title-group><journal-title>Cell host & microbe</journal-title>
</journal-title-group>
<issn pub-type="ppub">1931-3128</issn>
<issn pub-type="epub">1934-6069</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">25766295</article-id>
<article-id pub-id-type="pmc">4374348</article-id>
<article-id pub-id-type="doi">10.1016/j.chom.2015.02.005</article-id>
<article-id pub-id-type="manuscript">NIHMS665148</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Structure and receptor binding of the hemagglutinin from a human H6N1 influenza virus</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Tzarum</surname>
<given-names>Netanel</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>de Vries</surname>
<given-names>Robert P.</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhu</surname>
<given-names>Xueyong</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Yu</surname>
<given-names>Wenli</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>McBride</surname>
<given-names>Ryan</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Paulson</surname>
<given-names>James C.</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="aff" rid="A4">4</xref>
<xref rid="FN1" ref-type="author-notes">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wilson</surname>
<given-names>Ian A.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A5">5</xref>
<xref rid="FN1" ref-type="author-notes">*</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</aff>
<aff id="A2"><label>2</label>
Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</aff>
<aff id="A3"><label>3</label>
Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</aff>
<aff id="A4"><label>4</label>
Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</aff>
<aff id="A5"><label>5</label>
Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA</aff>
<author-notes><corresp id="FN1"><label>*</label>
Correspondence: <email>wilson@scripps.edu</email>
, <email>jpaulson@scripps.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>10</day>
<month>3</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="ppub"><day>11</day>
<month>3</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>11</day>
<month>3</month>
<year>2016</year>
</pub-date>
<volume>17</volume>
<issue>3</issue>
<fpage>369</fpage>
<lpage>376</lpage>
<pmc-comment>elocation-id from pubmed: 10.1016/j.chom.2015.02.005</pmc-comment>
<permissions><copyright-statement>© 2015 Published by Elsevier Inc.</copyright-statement>
<copyright-year>2015</copyright-year>
</permissions>
<abstract><title>SUMMARY</title>
<p id="P1">Avian influenza viruses that cause infection and are transmissible in humans involve changes in the receptor binding site (RBS) of the viral hemagglutinin (HA) that alter receptor preference from α2-3-linked (avian-like) to α2-6-linked (human-like) sialosides. A human case of avian-origin H6N1 influenza virus was recently reported, but the molecular mechanisms contributing to it crossing the species barrier are unknown. We find that, although the H6 HA RBS contains D190V and G228S substitutions that potentially promote human receptor binding, recombinant H6 HA preferentially binds α2-3-linked sialosides, indicating no adaptation to human receptors. Crystal structures of H6 HA with avian and human receptor analogs reveal that H6 HA preferentially interacts with avian receptor analogs. This binding mechanism differs from other HA subtypes due to a unique combination of RBS residues, highlighting additional variation in HA-receptor interactions and the challenges in predicting which influenza strains and subtypes can infect humans and cause pandemics.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>
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