Structural basis of neutralization by a human anti-severe acute respiratory syndrome spike protein antibody, 80R.
Identifieur interne : 002101 ( PubMed/Corpus ); précédent : 002100; suivant : 002102Structural basis of neutralization by a human anti-severe acute respiratory syndrome spike protein antibody, 80R.
Auteurs : William C. Hwang ; Yaqiong Lin ; Eugenio Santelli ; Jianhua Sui ; Lukasz Jaroszewski ; Boguslaw Stec ; Michael Farzan ; Wayne A. Marasco ; Robert C. LiddingtonSource :
- The Journal of biological chemistry [ 0021-9258 ] ; 2006.
English descriptors
- KwdEn :
- Antibodies, Viral (immunology), Antibodies, Viral (metabolism), Binding Sites, Crystallization, Crystallography, X-Ray, Humans, Membrane Glycoproteins (chemistry), Membrane Glycoproteins (immunology), Membrane Glycoproteins (metabolism), Models, Molecular, Neutralization Tests, Protein Binding, Protein Structure, Tertiary, SARS Virus (metabolism), Severe Acute Respiratory Syndrome, Spike Glycoprotein, Coronavirus, Viral Envelope Proteins (chemistry), Viral Envelope Proteins (immunology), Viral Envelope Proteins (metabolism).
- MESH :
- chemical , chemistry : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , immunology : Antibodies, Viral, Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , metabolism : Antibodies, Viral, Membrane Glycoproteins, Viral Envelope Proteins.
- metabolism : SARS Virus.
- Binding Sites, Crystallization, Crystallography, X-Ray, Humans, Models, Molecular, Neutralization Tests, Protein Binding, Protein Structure, Tertiary, Severe Acute Respiratory Syndrome, Spike Glycoprotein, Coronavirus.
Abstract
Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease that caused pandemic spread in 2003. The etiological agent of SARS is a novel coronavirus (SARS-CoV). The coronaviral surface spike protein S is a type I transmembrane glycoprotein that mediates initial host binding via the cell surface receptor angiotensin-converting enzyme 2 (ACE2), as well as the subsequent membrane fusion events required for cell entry. Here we report the crystal structure of the S1 receptor binding domain (RBD) in complex with a neutralizing antibody, 80R, at 2.3 A resolution, as well as the structure of the uncomplexed S1 RBD at 2.2 A resolution. We show that the 80R-binding epitope on the S1 RBD overlaps very closely with the ACE2-binding site, providing a rationale for the strong binding and broad neutralizing ability of the antibody. We provide a structural basis for the differential effects of certain mutations in the spike protein on 80R versus ACE2 binding, including escape mutants, which should facilitate the design of immunotherapeutics to treat a future SARS outbreak. We further show that the RBD of S1 forms dimers via an extensive interface that is disrupted in receptor- and antibody-bound crystal structures, and we propose a role for the dimer in virus stability and infectivity.
DOI: 10.1074/jbc.M603275200
PubMed: 16954221
Links to Exploration step
pubmed:16954221Le document en format XML
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Hwang</name><affiliation><nlm:affiliation>Infectious and Inflammatory Disease Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Lin, Yaqiong" sort="Lin, Yaqiong" uniqKey="Lin Y" first="Yaqiong" last="Lin">Yaqiong Lin</name></author><author><name sortKey="Santelli, Eugenio" sort="Santelli, Eugenio" uniqKey="Santelli E" first="Eugenio" last="Santelli">Eugenio Santelli</name></author><author><name sortKey="Sui, Jianhua" sort="Sui, Jianhua" uniqKey="Sui J" first="Jianhua" last="Sui">Jianhua Sui</name></author><author><name sortKey="Jaroszewski, Lukasz" sort="Jaroszewski, Lukasz" uniqKey="Jaroszewski L" first="Lukasz" last="Jaroszewski">Lukasz Jaroszewski</name></author><author><name sortKey="Stec, Boguslaw" sort="Stec, Boguslaw" uniqKey="Stec B" first="Boguslaw" last="Stec">Boguslaw Stec</name></author><author><name sortKey="Farzan, Michael" sort="Farzan, Michael" uniqKey="Farzan M" first="Michael" last="Farzan">Michael Farzan</name></author><author><name sortKey="Marasco, Wayne A" sort="Marasco, Wayne A" uniqKey="Marasco W" first="Wayne A" last="Marasco">Wayne A. Marasco</name></author><author><name sortKey="Liddington, Robert C" sort="Liddington, Robert C" uniqKey="Liddington R" first="Robert C" last="Liddington">Robert C. Liddington</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2006">2006</date><idno type="RBID">pubmed:16954221</idno><idno type="pmid">16954221</idno><idno type="doi">10.1074/jbc.M603275200</idno><idno type="wicri:Area/PubMed/Corpus">002101</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002101</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Structural basis of neutralization by a human anti-severe acute respiratory syndrome spike protein antibody, 80R.</title><author><name sortKey="Hwang, William C" sort="Hwang, William C" uniqKey="Hwang W" first="William C" last="Hwang">William C. Hwang</name><affiliation><nlm:affiliation>Infectious and Inflammatory Disease Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Lin, Yaqiong" sort="Lin, Yaqiong" uniqKey="Lin Y" first="Yaqiong" last="Lin">Yaqiong Lin</name></author><author><name sortKey="Santelli, Eugenio" sort="Santelli, Eugenio" uniqKey="Santelli E" first="Eugenio" last="Santelli">Eugenio Santelli</name></author><author><name sortKey="Sui, Jianhua" sort="Sui, Jianhua" uniqKey="Sui J" first="Jianhua" last="Sui">Jianhua Sui</name></author><author><name sortKey="Jaroszewski, Lukasz" sort="Jaroszewski, Lukasz" uniqKey="Jaroszewski L" first="Lukasz" last="Jaroszewski">Lukasz Jaroszewski</name></author><author><name sortKey="Stec, Boguslaw" sort="Stec, Boguslaw" uniqKey="Stec B" first="Boguslaw" last="Stec">Boguslaw Stec</name></author><author><name sortKey="Farzan, Michael" sort="Farzan, Michael" uniqKey="Farzan M" first="Michael" last="Farzan">Michael Farzan</name></author><author><name sortKey="Marasco, Wayne A" sort="Marasco, Wayne A" uniqKey="Marasco W" first="Wayne A" last="Marasco">Wayne A. Marasco</name></author><author><name sortKey="Liddington, Robert C" sort="Liddington, Robert C" uniqKey="Liddington R" first="Robert C" last="Liddington">Robert C. Liddington</name></author></analytic><series><title level="j">The Journal of biological chemistry</title><idno type="ISSN">0021-9258</idno><imprint><date when="2006" type="published">2006</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antibodies, Viral (immunology)</term><term>Antibodies, Viral (metabolism)</term><term>Binding Sites</term><term>Crystallization</term><term>Crystallography, X-Ray</term><term>Humans</term><term>Membrane Glycoproteins (chemistry)</term><term>Membrane Glycoproteins (immunology)</term><term>Membrane Glycoproteins (metabolism)</term><term>Models, Molecular</term><term>Neutralization Tests</term><term>Protein Binding</term><term>Protein Structure, Tertiary</term><term>SARS Virus (metabolism)</term><term>Severe Acute Respiratory Syndrome</term><term>Spike Glycoprotein, Coronavirus</term><term>Viral Envelope Proteins (chemistry)</term><term>Viral Envelope Proteins (immunology)</term><term>Viral Envelope Proteins (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Viral</term><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antibodies, Viral</term><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Binding Sites</term><term>Crystallization</term><term>Crystallography, X-Ray</term><term>Humans</term><term>Models, Molecular</term><term>Neutralization Tests</term><term>Protein Binding</term><term>Protein Structure, Tertiary</term><term>Severe Acute Respiratory Syndrome</term><term>Spike Glycoprotein, Coronavirus</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease that caused pandemic spread in 2003. The etiological agent of SARS is a novel coronavirus (SARS-CoV). The coronaviral surface spike protein S is a type I transmembrane glycoprotein that mediates initial host binding via the cell surface receptor angiotensin-converting enzyme 2 (ACE2), as well as the subsequent membrane fusion events required for cell entry. Here we report the crystal structure of the S1 receptor binding domain (RBD) in complex with a neutralizing antibody, 80R, at 2.3 A resolution, as well as the structure of the uncomplexed S1 RBD at 2.2 A resolution. We show that the 80R-binding epitope on the S1 RBD overlaps very closely with the ACE2-binding site, providing a rationale for the strong binding and broad neutralizing ability of the antibody. We provide a structural basis for the differential effects of certain mutations in the spike protein on 80R versus ACE2 binding, including escape mutants, which should facilitate the design of immunotherapeutics to treat a future SARS outbreak. We further show that the RBD of S1 forms dimers via an extensive interface that is disrupted in receptor- and antibody-bound crystal structures, and we propose a role for the dimer in virus stability and infectivity.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">16954221</PMID><DateCompleted><Year>2006</Year><Month>12</Month><Day>21</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Print">0021-9258</ISSN><JournalIssue CitedMedium="Print"><Volume>281</Volume><Issue>45</Issue><PubDate><Year>2006</Year><Month>Nov</Month><Day>10</Day></PubDate></JournalIssue><Title>The Journal of biological chemistry</Title><ISOAbbreviation>J. Biol. Chem.</ISOAbbreviation></Journal><ArticleTitle>Structural basis of neutralization by a human anti-severe acute respiratory syndrome spike protein antibody, 80R.</ArticleTitle><Pagination><MedlinePgn>34610-6</MedlinePgn></Pagination><Abstract><AbstractText>Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease that caused pandemic spread in 2003. The etiological agent of SARS is a novel coronavirus (SARS-CoV). The coronaviral surface spike protein S is a type I transmembrane glycoprotein that mediates initial host binding via the cell surface receptor angiotensin-converting enzyme 2 (ACE2), as well as the subsequent membrane fusion events required for cell entry. Here we report the crystal structure of the S1 receptor binding domain (RBD) in complex with a neutralizing antibody, 80R, at 2.3 A resolution, as well as the structure of the uncomplexed S1 RBD at 2.2 A resolution. We show that the 80R-binding epitope on the S1 RBD overlaps very closely with the ACE2-binding site, providing a rationale for the strong binding and broad neutralizing ability of the antibody. We provide a structural basis for the differential effects of certain mutations in the spike protein on 80R versus ACE2 binding, including escape mutants, which should facilitate the design of immunotherapeutics to treat a future SARS outbreak. We further show that the RBD of S1 forms dimers via an extensive interface that is disrupted in receptor- and antibody-bound crystal structures, and we propose a role for the dimer in virus stability and infectivity.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hwang</LastName><ForeName>William C</ForeName><Initials>WC</Initials><AffiliationInfo><Affiliation>Infectious and Inflammatory Disease Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lin</LastName><ForeName>Yaqiong</ForeName><Initials>Y</Initials></Author><Author ValidYN="Y"><LastName>Santelli</LastName><ForeName>Eugenio</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Sui</LastName><ForeName>Jianhua</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Jaroszewski</LastName><ForeName>Lukasz</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Stec</LastName><ForeName>Boguslaw</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Farzan</LastName><ForeName>Michael</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Marasco</LastName><ForeName>Wayne A</ForeName><Initials>WA</Initials></Author><Author ValidYN="Y"><LastName>Liddington</LastName><ForeName>Robert C</ForeName><Initials>RC</Initials></Author></AuthorList><Language>eng</Language><DataBankList CompleteYN="Y"><DataBank><DataBankName>PDB</DataBankName><AccessionNumberList><AccessionNumber>2GHV</AccessionNumber><AccessionNumber>2GHW</AccessionNumber></AccessionNumberList></DataBank></DataBankList><GrantList CompleteYN="Y"><Grant><GrantID>AI053822</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AI061318</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AI28785</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AI48436</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="D013486">Research Support, U.S. Gov't, Non-P.H.S.</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2006</Year><Month>09</Month><Day>05</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Biol Chem</MedlineTA><NlmUniqueID>2985121R</NlmUniqueID><ISSNLinking>0021-9258</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000914">Antibodies, 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