A virus-binding hot spot on human angiotensin-converting enzyme 2 is critical for binding of two different coronaviruses.
Identifieur interne : 001538 ( PubMed/Corpus ); précédent : 001537; suivant : 001539A 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 LiSource :
- Journal of virology [ 1098-5514 ] ; 2011.
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Peptidyl-Dipeptidase A, Receptors, Virus.
- chemical , metabolism : Peptidyl-Dipeptidase A, Receptors, Virus.
- physiology : Coronavirus NL63, Human, SARS Virus.
- DNA Mutational Analysis, Humans, Protein Binding, Transduction, Genetic, Virus Attachment.
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.
DOI: 10.1128/JVI.02274-10
PubMed: 21411533
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pubmed:21411533Le document en format XML
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Pennell</name></author><author><name sortKey="Mansky, Louis M" sort="Mansky, Louis M" uniqKey="Mansky L" first="Louis M" last="Mansky">Louis M. Mansky</name></author><author><name sortKey="Geraghty, Robert J" sort="Geraghty, Robert J" uniqKey="Geraghty R" first="Robert J" last="Geraghty">Robert J. Geraghty</name></author><author><name sortKey="Li, Fang" sort="Li, Fang" uniqKey="Li F" first="Fang" last="Li">Fang Li</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2011">2011</date><idno type="RBID">pubmed:21411533</idno><idno type="pmid">21411533</idno><idno type="doi">10.1128/JVI.02274-10</idno><idno type="wicri:Area/PubMed/Corpus">001538</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001538</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A virus-binding hot spot on human angiotensin-converting enzyme 2 is critical for binding of two different coronaviruses.</title><author><name sortKey="Wu, Kailang" sort="Wu, Kailang" uniqKey="Wu K" first="Kailang" last="Wu">Kailang Wu</name><affiliation><nlm:affiliation>Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Chen, Lang" sort="Chen, Lang" uniqKey="Chen L" first="Lang" last="Chen">Lang Chen</name></author><author><name sortKey="Peng, Guiqing" sort="Peng, Guiqing" uniqKey="Peng G" first="Guiqing" last="Peng">Guiqing Peng</name></author><author><name sortKey="Zhou, Wenbo" sort="Zhou, Wenbo" uniqKey="Zhou W" first="Wenbo" last="Zhou">Wenbo Zhou</name></author><author><name sortKey="Pennell, Christopher A" sort="Pennell, Christopher A" uniqKey="Pennell C" first="Christopher A" last="Pennell">Christopher A. Pennell</name></author><author><name sortKey="Mansky, Louis M" sort="Mansky, Louis M" uniqKey="Mansky L" first="Louis M" last="Mansky">Louis M. Mansky</name></author><author><name sortKey="Geraghty, Robert J" sort="Geraghty, Robert J" uniqKey="Geraghty R" first="Robert J" last="Geraghty">Robert J. Geraghty</name></author><author><name sortKey="Li, Fang" sort="Li, Fang" uniqKey="Li F" first="Fang" last="Li">Fang Li</name></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2011" type="published">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Coronavirus NL63, Human (physiology)</term><term>DNA Mutational Analysis</term><term>Humans</term><term>Peptidyl-Dipeptidase A (genetics)</term><term>Peptidyl-Dipeptidase A (metabolism)</term><term>Protein Binding</term><term>Receptors, Virus (genetics)</term><term>Receptors, Virus (metabolism)</term><term>SARS Virus (physiology)</term><term>Transduction, Genetic</term><term>Virus Attachment</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Peptidyl-Dipeptidase A</term><term>Receptors, Virus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Peptidyl-Dipeptidase A</term><term>Receptors, Virus</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Coronavirus NL63, Human</term><term>SARS Virus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>DNA Mutational Analysis</term><term>Humans</term><term>Protein Binding</term><term>Transduction, Genetic</term><term>Virus Attachment</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">21411533</PMID><DateCompleted><Year>2011</Year><Month>07</Month><Day>13</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1098-5514</ISSN><JournalIssue CitedMedium="Internet"><Volume>85</Volume><Issue>11</Issue><PubDate><Year>2011</Year><Month>Jun</Month></PubDate></JournalIssue><Title>Journal of virology</Title><ISOAbbreviation>J. Virol.</ISOAbbreviation></Journal><ArticleTitle>A virus-binding hot spot on human angiotensin-converting enzyme 2 is critical for binding of two different coronaviruses.</ArticleTitle><Pagination><MedlinePgn>5331-7</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1128/JVI.02274-10</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Kailang</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Lang</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Peng</LastName><ForeName>Guiqing</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Zhou</LastName><ForeName>Wenbo</ForeName><Initials>W</Initials></Author><Author ValidYN="Y"><LastName>Pennell</LastName><ForeName>Christopher A</ForeName><Initials>CA</Initials></Author><Author ValidYN="Y"><LastName>Mansky</LastName><ForeName>Louis M</ForeName><Initials>LM</Initials></Author><Author ValidYN="Y"><LastName>Geraghty</LastName><ForeName>Robert J</ForeName><Initials>RJ</Initials></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Fang</ForeName><Initials>F</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 AI089728</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01AI089728</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2011</Year><Month>03</Month><Day>16</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Virol</MedlineTA><NlmUniqueID>0113724</NlmUniqueID><ISSNLinking>0022-538X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011991">Receptors, Virus</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.15.1</RegistryNumber><NameOfSubstance UI="D007703">Peptidyl-Dipeptidase A</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.17.-</RegistryNumber><NameOfSubstance UI="C413524">angiotensin converting enzyme 2</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D058957" MajorTopicYN="N">Coronavirus NL63, Human</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004252" MajorTopicYN="N">DNA Mutational Analysis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007703" MajorTopicYN="N">Peptidyl-Dipeptidase A</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011485" MajorTopicYN="N">Protein Binding</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011991" MajorTopicYN="N">Receptors, Virus</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D045473" MajorTopicYN="N">SARS Virus</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014161" MajorTopicYN="N">Transduction, Genetic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D053585" 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