SrasV1, Pmc, Corpus, bibRecord, 000C65

A Virus-Binding Hot Spot on Human Angiotensin-Converting Enzyme 2 Is Critical for Binding of Two Different Coronaviruses▿

Identifieur interne : 000C65 ( Pmc/Corpus ); précédent : 000C64; suivant : 000C66

A Virus-Binding Hot Spot on Human Angiotensin-Converting Enzyme 2 Is Critical for Binding of Two Different Coronaviruses▿

Auteurs : Kailang Wu ; Lang Chen ; Guiqing Peng ; Wenbo Zhou ; Christopher A. Pennell ; Louis M. Mansky ; Robert J. Geraghty ; Fang Li

Source :

Journal of Virology [ 0022-538X ] ; 2011.

RBID : PMC:3094985

Abstract

How viruses evolve to select their receptor proteins for host cell entry is puzzling. We recently determined the crystal structures of NL63 coronavirus (NL63-CoV) and SARS coronavirus (SARS-CoV) receptor-binding domains (RBDs), each complexed with their common receptor, human angiotensin-converting enzyme 2 (hACE2), and proposed the existence of a virus-binding hot spot on hACE2. Here we investigated the function of this hypothetical hot spot using structure-guided biochemical and functional assays. The hot spot consists of a salt bridge surrounded by hydrophobic tunnel walls. Mutations that disturb the hot spot structure have significant effects on virus/receptor interactions, revealing critical energy contributions from the hot spot structure. The tunnel structure at the NL63-CoV/hACE2 interface is more compact than that at the SARS-CoV/hACE2 interface, and hence RBD/hACE2 binding affinities are decreased either by NL63-CoV mutations decreasing the tunnel space or by SARS-CoV mutations increasing the tunnel space. Furthermore, NL63-CoV RBD inhibits hACE2-dependent transduction by SARS-CoV spike protein, a successful application of the hot spot theory that has the potential to become a new antiviral strategy against SARS-CoV infections. These results suggest that the structural features of the hot spot on hACE2 were among the driving forces for the convergent evolution of NL63-CoV and SARS-CoV.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3094985

DOI: 10.1128/JVI.02274-10
PubMed: 21411533
PubMed Central: 3094985

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PMC:3094985

Le document en format XML

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<author><name sortKey="Wu, Kailang" sort="Wu, Kailang" uniqKey="Wu K" first="Kailang" last="Wu">Kailang Wu</name>
<affiliation><nlm:aff id="aff1">Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455</nlm:aff>
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<author><name sortKey="Chen, Lang" sort="Chen, Lang" uniqKey="Chen L" first="Lang" last="Chen">Lang Chen</name>
<affiliation><nlm:aff id="aff1">Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455</nlm:aff>
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<author><name sortKey="Peng, Guiqing" sort="Peng, Guiqing" uniqKey="Peng G" first="Guiqing" last="Peng">Guiqing Peng</name>
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<author><name sortKey="Zhou, Wenbo" sort="Zhou, Wenbo" uniqKey="Zhou W" first="Wenbo" last="Zhou">Wenbo Zhou</name>
<affiliation><nlm:aff id="aff2">Center for Drug Design, University of Minnesota, Minneapolis, Minnesota 55455</nlm:aff>
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<author><name sortKey="Pennell, Christopher A" sort="Pennell, Christopher A" uniqKey="Pennell C" first="Christopher A." last="Pennell">Christopher A. Pennell</name>
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<author><name sortKey="Mansky, Louis M" sort="Mansky, Louis M" uniqKey="Mansky L" first="Louis M." last="Mansky">Louis M. Mansky</name>
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<author><name sortKey="Geraghty, Robert J" sort="Geraghty, Robert J" uniqKey="Geraghty R" first="Robert J." last="Geraghty">Robert J. Geraghty</name>
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<author><name sortKey="Li, Fang" sort="Li, Fang" uniqKey="Li F" first="Fang" last="Li">Fang Li</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A Virus-Binding Hot Spot on Human Angiotensin-Converting Enzyme 2 Is Critical for Binding of Two Different Coronaviruses<xref ref-type="fn" rid="FN1"><sup>▿</sup>
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<author><name sortKey="Wu, Kailang" sort="Wu, Kailang" uniqKey="Wu K" first="Kailang" last="Wu">Kailang Wu</name>
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<author><name sortKey="Chen, Lang" sort="Chen, Lang" uniqKey="Chen L" first="Lang" last="Chen">Lang Chen</name>
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<author><name sortKey="Peng, Guiqing" sort="Peng, Guiqing" uniqKey="Peng G" first="Guiqing" last="Peng">Guiqing Peng</name>
<affiliation><nlm:aff id="aff1">Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455</nlm:aff>
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<author><name sortKey="Zhou, Wenbo" sort="Zhou, Wenbo" uniqKey="Zhou W" first="Wenbo" last="Zhou">Wenbo Zhou</name>
<affiliation><nlm:aff id="aff2">Center for Drug Design, University of Minnesota, Minneapolis, Minnesota 55455</nlm:aff>
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<author><name sortKey="Pennell, Christopher A" sort="Pennell, Christopher A" uniqKey="Pennell C" first="Christopher A." last="Pennell">Christopher A. Pennell</name>
<affiliation><nlm:aff id="aff3">Cancer Center, Center for Immunology, University of Minnesota, Minneapolis, Minnesota 55455</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mansky, Louis M" sort="Mansky, Louis M" uniqKey="Mansky L" first="Louis M." last="Mansky">Louis M. Mansky</name>
<affiliation><nlm:aff id="aff4">Institute for Molecular Virology and Departments of Diagnostic and Biological Sciences and Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455</nlm:aff>
</affiliation>
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<author><name sortKey="Geraghty, Robert J" sort="Geraghty, Robert J" uniqKey="Geraghty R" first="Robert J." last="Geraghty">Robert J. Geraghty</name>
<affiliation><nlm:aff id="aff2">Center for Drug Design, University of Minnesota, Minneapolis, Minnesota 55455</nlm:aff>
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<author><name sortKey="Li, Fang" sort="Li, Fang" uniqKey="Li F" first="Fang" last="Li">Fang Li</name>
<affiliation><nlm:aff id="aff1">Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455</nlm:aff>
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<series><title level="j">Journal of Virology</title>
<idno type="ISSN">0022-538X</idno>
<idno type="eISSN">1098-5514</idno>
<imprint><date when="2011">2011</date>
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<front><div type="abstract" xml:lang="en"><p>How viruses evolve to select their receptor proteins for host cell entry is puzzling. We recently determined the crystal structures of NL63 coronavirus (NL63-CoV) and SARS coronavirus (SARS-CoV) receptor-binding domains (RBDs), each complexed with their common receptor, human angiotensin-converting enzyme 2 (hACE2), and proposed the existence of a virus-binding hot spot on hACE2. Here we investigated the function of this hypothetical hot spot using structure-guided biochemical and functional assays. The hot spot consists of a salt bridge surrounded by hydrophobic tunnel walls. Mutations that disturb the hot spot structure have significant effects on virus/receptor interactions, revealing critical energy contributions from the hot spot structure. The tunnel structure at the NL63-CoV/hACE2 interface is more compact than that at the SARS-CoV/hACE2 interface, and hence RBD/hACE2 binding affinities are decreased either by NL63-CoV mutations decreasing the tunnel space or by SARS-CoV mutations increasing the tunnel space. Furthermore, NL63-CoV RBD inhibits hACE2-dependent transduction by SARS-CoV spike protein, a successful application of the hot spot theory that has the potential to become a new antiviral strategy against SARS-CoV infections. These results suggest that the structural features of the hot spot on hACE2 were among the driving forces for the convergent evolution of NL63-CoV and SARS-CoV.</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="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>
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<article-meta><article-id pub-id-type="pmid">21411533</article-id>
<article-id pub-id-type="pmc">3094985</article-id>
<article-id pub-id-type="publisher-id">2274-10</article-id>
<article-id pub-id-type="doi">10.1128/JVI.02274-10</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Virus-Cell Interactions</subject>
</subj-group>
</article-categories>
<title-group><article-title>A Virus-Binding Hot Spot on Human Angiotensin-Converting Enzyme 2 Is Critical for Binding of Two Different Coronaviruses<xref ref-type="fn" rid="FN1"><sup>▿</sup>
</xref>
</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Wu</surname>
<given-names>Kailang</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chen</surname>
<given-names>Lang</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Peng</surname>
<given-names>Guiqing</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhou</surname>
<given-names>Wenbo</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pennell</surname>
<given-names>Christopher A.</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mansky</surname>
<given-names>Louis M.</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Geraghty</surname>
<given-names>Robert J.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Li</surname>
<given-names>Fang</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
<aff id="aff1"><label>1</label>
Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455</aff>
<aff id="aff2"><label>2</label>
Center for Drug Design, University of Minnesota, Minneapolis, Minnesota 55455</aff>
<aff id="aff3"><label>3</label>
Cancer Center, Center for Immunology, University of Minnesota, Minneapolis, Minnesota 55455</aff>
<aff id="aff4"><label>4</label>
Institute for Molecular Virology and Departments of Diagnostic and Biological Sciences and Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455</aff>
</contrib-group>
<author-notes><corresp id="cor1"><label>*</label>
Corresponding author. Mailing address: <addr-line>Department of Pharmacology, University of Minnesota Medical School, 6-121 Jackson Hall, 321 Church St. SE, Minneapolis, MN 55455</addr-line>
. Phone: <phone>(612) 625-6149</phone>
. Fax: <fax>(612) 625-8408</fax>
. E-mail: <email>lifang@umn.edu</email>
.</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>6</month>
<year>2011</year>
</pub-date>
<volume>85</volume>
<issue>11</issue>
<fpage>5331</fpage>
<lpage>5337</lpage>
<history><date date-type="received"><day>29</day>
<month>10</month>
<year>2010</year>
</date>
<date date-type="accepted"><day>2</day>
<month>3</month>
<year>2011</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2011, American Society for Microbiology</copyright-statement>
<copyright-year>2011</copyright-year>
<copyright-holder>American Society for Microbiology</copyright-holder>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zjv01111005331.pdf"></self-uri>
<abstract><p>How viruses evolve to select their receptor proteins for host cell entry is puzzling. We recently determined the crystal structures of NL63 coronavirus (NL63-CoV) and SARS coronavirus (SARS-CoV) receptor-binding domains (RBDs), each complexed with their common receptor, human angiotensin-converting enzyme 2 (hACE2), and proposed the existence of a virus-binding hot spot on hACE2. Here we investigated the function of this hypothetical hot spot using structure-guided biochemical and functional assays. The hot spot consists of a salt bridge surrounded by hydrophobic tunnel walls. Mutations that disturb the hot spot structure have significant effects on virus/receptor interactions, revealing critical energy contributions from the hot spot structure. The tunnel structure at the NL63-CoV/hACE2 interface is more compact than that at the SARS-CoV/hACE2 interface, and hence RBD/hACE2 binding affinities are decreased either by NL63-CoV mutations decreasing the tunnel space or by SARS-CoV mutations increasing the tunnel space. Furthermore, NL63-CoV RBD inhibits hACE2-dependent transduction by SARS-CoV spike protein, a successful application of the hot spot theory that has the potential to become a new antiviral strategy against SARS-CoV infections. These results suggest that the structural features of the hot spot on hACE2 were among the driving forces for the convergent evolution of NL63-CoV and SARS-CoV.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>

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A Virus-Binding Hot Spot on Human Angiotensin-Converting Enzyme 2 Is Critical for Binding of Two Different Coronaviruses▿

A Virus-Binding Hot Spot on Human Angiotensin-Converting Enzyme 2 Is Critical for Binding of Two Different Coronaviruses▿

Source :

Abstract

Links to Exploration step

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