Structural basis of neutralization by a human anti-severe acute respiratory syndrome spike protein antibody, 80R.
Identifieur interne : 003C93 ( Main/Exploration ); précédent : 003C92; suivant : 003C94Structural basis of neutralization by a human anti-severe acute respiratory syndrome spike protein antibody, 80R.
Auteurs : William C. Hwang [États-Unis] ; 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.
Descripteurs français
- KwdFr :
- Anticorps antiviraux (immunologie), Anticorps antiviraux (métabolisme), Cristallisation, Cristallographie aux rayons X, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (), Glycoprotéines membranaires (immunologie), Glycoprotéines membranaires (métabolisme), Humains, Liaison aux protéines, Modèles moléculaires, Protéines de l'enveloppe virale (), Protéines de l'enveloppe virale (immunologie), Protéines de l'enveloppe virale (métabolisme), Sites de fixation, Structure tertiaire des protéines, Syndrome respiratoire aigu sévère, Tests de neutralisation, Virus du SRAS (métabolisme).
- MESH :
- immunologie : Anticorps antiviraux, Glycoprotéines membranaires, Protéines de l'enveloppe virale.
- métabolisme : Anticorps antiviraux, Glycoprotéines membranaires, Protéines de l'enveloppe virale, Virus du SRAS.
- Cristallisation, Cristallographie aux rayons X, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires, Humains, Liaison aux protéines, Modèles moléculaires, Protéines de l'enveloppe virale, Sites de fixation, Structure tertiaire des protéines, Syndrome respiratoire aigu sévère, Tests de neutralisation.
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
Affiliations:
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Le document en format XML
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<term>Crystallography, X-Ray</term>
<term>Humans</term>
<term>Membrane Glycoproteins (chemistry)</term>
<term>Membrane Glycoproteins (immunology)</term>
<term>Membrane Glycoproteins (metabolism)</term>
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<term>Anticorps antiviraux (métabolisme)</term>
<term>Cristallisation</term>
<term>Cristallographie aux rayons X</term>
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<term>Glycoprotéines membranaires ()</term>
<term>Glycoprotéines membranaires (immunologie)</term>
<term>Glycoprotéines membranaires (métabolisme)</term>
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<term>Modèles moléculaires</term>
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<term>Structure tertiaire des protéines</term>
<term>Syndrome respiratoire aigu sévère</term>
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<term>Viral Envelope Proteins</term>
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<term>Protéines de l'enveloppe virale</term>
<term>Virus du SRAS</term>
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<term>Crystallography, X-Ray</term>
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<term>Models, Molecular</term>
<term>Neutralization Tests</term>
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<term>Protein Structure, Tertiary</term>
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<term>Liaison aux protéines</term>
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<term>Protéines de l'enveloppe virale</term>
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<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>
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<name sortKey="Liddington, Robert C" sort="Liddington, Robert C" uniqKey="Liddington R" first="Robert C" last="Liddington">Robert C. Liddington</name>
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<name sortKey="Marasco, Wayne A" sort="Marasco, Wayne A" uniqKey="Marasco W" first="Wayne A" last="Marasco">Wayne A. Marasco</name>
<name sortKey="Santelli, Eugenio" sort="Santelli, Eugenio" uniqKey="Santelli E" first="Eugenio" last="Santelli">Eugenio Santelli</name>
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<name sortKey="Sui, Jianhua" sort="Sui, Jianhua" uniqKey="Sui J" first="Jianhua" last="Sui">Jianhua Sui</name>
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<country name="États-Unis"><noRegion><name sortKey="Hwang, William C" sort="Hwang, William C" uniqKey="Hwang W" first="William C" last="Hwang">William C. Hwang</name>
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