Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein.
Identifieur interne : 000839 ( PubMed/Curation ); précédent : 000838; suivant : 000840Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein.
Auteurs : Senyan Zhang [République populaire de Chine] ; Panpan Zhou [République populaire de Chine] ; Pengfei Wang [République populaire de Chine] ; Yangyang Li [République populaire de Chine] ; Liwei Jiang [République populaire de Chine] ; Wenxu Jia [République populaire de Chine] ; Han Wang [République populaire de Chine] ; Angela Fan [République populaire de Chine] ; Dongli Wang [République populaire de Chine] ; Xuanling Shi [République populaire de Chine] ; Xianyang Fang [République populaire de Chine] ; Michal Hammel [États-Unis] ; Shuying Wang [Taïwan] ; Xinquan Wang [République populaire de Chine] ; Linqi Zhang [République populaire de Chine]Source :
- Cell reports [ 2211-1247 ] ; 2018.
Descripteurs français
- KwdFr :
- Anticorps neutralisants (métabolisme), Coronavirus du syndrome respiratoire du Moyen-Orient (), Coronavirus du syndrome respiratoire du Moyen-Orient (génétique), Domaines protéiques, Glycoprotéine de spicule des coronavirus (), Humains, Liaison aux protéines, Modèles moléculaires, Multimérisation de protéines, Mutation (génétique), Sites de fixation, Épitopes ().
- MESH :
- génétique : Coronavirus du syndrome respiratoire du Moyen-Orient, Mutation.
- métabolisme : Anticorps neutralisants.
- Coronavirus du syndrome respiratoire du Moyen-Orient, Domaines protéiques, Glycoprotéine de spicule des coronavirus, Humains, Liaison aux protéines, Modèles moléculaires, Multimérisation de protéines, Sites de fixation, Épitopes.
English descriptors
- KwdEn :
- Antibodies, Neutralizing (metabolism), Binding Sites, Epitopes (chemistry), Humans, Middle East Respiratory Syndrome Coronavirus (chemistry), Middle East Respiratory Syndrome Coronavirus (genetics), Models, Molecular, Mutation (genetics), Protein Binding, Protein Domains, Protein Multimerization, Spike Glycoprotein, Coronavirus (chemistry).
- MESH :
- chemical , chemistry : Epitopes, Spike Glycoprotein, Coronavirus.
- chemical , metabolism : Antibodies, Neutralizing.
- chemistry : Middle East Respiratory Syndrome Coronavirus.
- genetics : Middle East Respiratory Syndrome Coronavirus, Mutation.
- Binding Sites, Humans, Models, Molecular, Protein Binding, Protein Domains, Protein Multimerization.
Abstract
The major mechanism of antibody-mediated neutralization of the Middle East respiratory syndrome coronavirus (MERS-CoV) involves competition with the cellular receptor dipeptidyl peptidase 4 (DPP4) for binding to the receptor-binding domain (RBD) of the spike (S) glycoprotein. Here, we report a unique epitope and unusual neutralizing mechanism of the isolated human antibody MERS-4. Structurally, MERS-4 approached the RBD from the outside of the RBD-DPP4 binding interface. Such binding resulted in the folding of the β5-β6 loop toward a shallow groove on the RBD interface critical for accommodating DPP4. The key residues for binding are identified through site-directed mutagenesis. Structural modeling revealed that MERS-4 binds to RBD only in the "up" position in the S trimer. Furthermore, MERS-4 demonstrated synergy with several reported antibodies. These results indicate that MERS-4 neutralizes MERS-CoV by indirect rather than direct competition with DPP4. This mechanism provides a valuable addition for the combined use of antibodies against MERS-CoV infection.
DOI: 10.1016/j.celrep.2018.06.041
PubMed: 29996104
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Panpan" sort="Zhou, Panpan" uniqKey="Zhou P" first="Panpan" last="Zhou">Panpan Zhou</name><affiliation wicri:level="1"><nlm:affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Pengfei" sort="Wang, Pengfei" uniqKey="Wang P" first="Pengfei" last="Wang">Pengfei Wang</name><affiliation wicri:level="1"><nlm:affiliation>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084</wicri:regionArea></affiliation></author><author><name sortKey="Li, Yangyang" sort="Li, Yangyang" uniqKey="Li Y" first="Yangyang" last="Li">Yangyang Li</name><affiliation wicri:level="1"><nlm:affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Comprehensive AIDS Research 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Wenxu" sort="Jia, Wenxu" uniqKey="Jia W" first="Wenxu" last="Jia">Wenxu Jia</name><affiliation wicri:level="1"><nlm:affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Han" sort="Wang, Han" uniqKey="Wang H" first="Han" last="Wang">Han Wang</name><affiliation wicri:level="1"><nlm:affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084</wicri:regionArea></affiliation></author><author><name sortKey="Fan, Angela" sort="Fan, Angela" uniqKey="Fan A" first="Angela" last="Fan">Angela Fan</name><affiliation wicri:level="1"><nlm:affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Dongli" sort="Wang, Dongli" uniqKey="Wang D" first="Dongli" last="Wang">Dongli Wang</name><affiliation wicri:level="1"><nlm:affiliation>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084</wicri:regionArea></affiliation></author><author><name sortKey="Shi, Xuanling" sort="Shi, Xuanling" uniqKey="Shi X" first="Xuanling" last="Shi">Xuanling Shi</name><affiliation wicri:level="1"><nlm:affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084</wicri:regionArea></affiliation></author><author><name sortKey="Fang, Xianyang" sort="Fang, Xianyang" uniqKey="Fang X" first="Xianyang" last="Fang">Xianyang Fang</name><affiliation wicri:level="1"><nlm:affiliation>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation 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Shuying" sort="Wang, Shuying" uniqKey="Wang S" first="Shuying" last="Wang">Shuying Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan 701, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan 701</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Xinquan" sort="Wang, Xinquan" uniqKey="Wang X" first="Xinquan" last="Wang">Xinquan Wang</name><affiliation wicri:level="1"><nlm:affiliation>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China; Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. Electronic address: xinquanwang@mail.tsinghua.edu.cn.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China; Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Linqi" sort="Zhang, Linqi" uniqKey="Zhang L" first="Linqi" last="Zhang">Linqi Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China. 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xml:lang="en">Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein.</title><author><name sortKey="Zhang, Senyan" sort="Zhang, Senyan" uniqKey="Zhang S" first="Senyan" last="Zhang">Senyan Zhang</name><affiliation wicri:level="1"><nlm:affiliation>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084</wicri:regionArea></affiliation></author><author><name sortKey="Zhou, Panpan" sort="Zhou, Panpan" uniqKey="Zhou P" first="Panpan" last="Zhou">Panpan Zhou</name><affiliation wicri:level="1"><nlm:affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Pengfei" sort="Wang, Pengfei" uniqKey="Wang P" first="Pengfei" last="Wang">Pengfei Wang</name><affiliation wicri:level="1"><nlm:affiliation>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084</wicri:regionArea></affiliation></author><author><name sortKey="Li, Yangyang" sort="Li, Yangyang" uniqKey="Li Y" first="Yangyang" last="Li">Yangyang Li</name><affiliation wicri:level="1"><nlm:affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084</wicri:regionArea></affiliation></author><author><name sortKey="Jiang, Liwei" sort="Jiang, Liwei" uniqKey="Jiang L" first="Liwei" last="Jiang">Liwei Jiang</name><affiliation wicri:level="1"><nlm:affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084</wicri:regionArea></affiliation></author><author><name sortKey="Jia, Wenxu" sort="Jia, Wenxu" uniqKey="Jia W" first="Wenxu" last="Jia">Wenxu Jia</name><affiliation wicri:level="1"><nlm:affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Han" sort="Wang, Han" uniqKey="Wang H" first="Han" last="Wang">Han Wang</name><affiliation wicri:level="1"><nlm:affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084</wicri:regionArea></affiliation></author><author><name sortKey="Fan, Angela" sort="Fan, Angela" uniqKey="Fan A" first="Angela" last="Fan">Angela Fan</name><affiliation wicri:level="1"><nlm:affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Dongli" sort="Wang, Dongli" uniqKey="Wang D" first="Dongli" last="Wang">Dongli Wang</name><affiliation wicri:level="1"><nlm:affiliation>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084</wicri:regionArea></affiliation></author><author><name sortKey="Shi, Xuanling" sort="Shi, Xuanling" uniqKey="Shi X" first="Xuanling" last="Shi">Xuanling Shi</name><affiliation wicri:level="1"><nlm:affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084</wicri:regionArea></affiliation></author><author><name sortKey="Fang, Xianyang" sort="Fang, Xianyang" uniqKey="Fang X" first="Xianyang" last="Fang">Xianyang Fang</name><affiliation wicri:level="1"><nlm:affiliation>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084</wicri:regionArea></affiliation></author><author><name sortKey="Hammel, Michal" sort="Hammel, Michal" uniqKey="Hammel M" first="Michal" last="Hammel">Michal Hammel</name><affiliation wicri:level="1"><nlm:affiliation>Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA 94720</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Shuying" sort="Wang, Shuying" uniqKey="Wang S" first="Shuying" last="Wang">Shuying Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan 701, Taiwan.</nlm:affiliation><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan 701</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Xinquan" sort="Wang, Xinquan" uniqKey="Wang X" first="Xinquan" last="Wang">Xinquan Wang</name><affiliation wicri:level="1"><nlm:affiliation>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China; Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. Electronic address: xinquanwang@mail.tsinghua.edu.cn.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China; Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Linqi" sort="Zhang, Linqi" uniqKey="Zhang L" first="Linqi" last="Zhang">Linqi Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China. Electronic address: zhanglinqi@mail.tsinghua.edu.cn.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084</wicri:regionArea></affiliation></author></analytic><series><title level="j">Cell reports</title><idno type="eISSN">2211-1247</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antibodies, Neutralizing (metabolism)</term><term>Binding Sites</term><term>Epitopes (chemistry)</term><term>Humans</term><term>Middle East Respiratory Syndrome Coronavirus (chemistry)</term><term>Middle East Respiratory Syndrome Coronavirus (genetics)</term><term>Models, Molecular</term><term>Mutation (genetics)</term><term>Protein Binding</term><term>Protein Domains</term><term>Protein Multimerization</term><term>Spike Glycoprotein, Coronavirus (chemistry)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Anticorps neutralisants (métabolisme)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient ()</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (génétique)</term><term>Domaines protéiques</term><term>Glycoprotéine de spicule des coronavirus ()</term><term>Humains</term><term>Liaison aux protéines</term><term>Modèles moléculaires</term><term>Multimérisation de protéines</term><term>Mutation (génétique)</term><term>Sites de fixation</term><term>Épitopes ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Epitopes</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antibodies, Neutralizing</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term><term>Mutation</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Mutation</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Anticorps neutralisants</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Binding Sites</term><term>Humans</term><term>Models, Molecular</term><term>Protein Binding</term><term>Protein Domains</term><term>Protein Multimerization</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Domaines protéiques</term><term>Glycoprotéine de spicule des coronavirus</term><term>Humains</term><term>Liaison aux protéines</term><term>Modèles moléculaires</term><term>Multimérisation de protéines</term><term>Sites de fixation</term><term>Épitopes</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The major mechanism of antibody-mediated neutralization of the Middle East respiratory syndrome coronavirus (MERS-CoV) involves competition with the cellular receptor dipeptidyl peptidase 4 (DPP4) for binding to the receptor-binding domain (RBD) of the spike (S) glycoprotein. Here, we report a unique epitope and unusual neutralizing mechanism of the isolated human antibody MERS-4. Structurally, MERS-4 approached the RBD from the outside of the RBD-DPP4 binding interface. Such binding resulted in the folding of the β5-β6 loop toward a shallow groove on the RBD interface critical for accommodating DPP4. The key residues for binding are identified through site-directed mutagenesis. Structural modeling revealed that MERS-4 binds to RBD only in the "up" position in the S trimer. Furthermore, MERS-4 demonstrated synergy with several reported antibodies. These results indicate that MERS-4 neutralizes MERS-CoV by indirect rather than direct competition with DPP4. This mechanism provides a valuable addition for the combined use of antibodies against MERS-CoV infection.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">29996104</PMID><DateCompleted><Year>2019</Year><Month>11</Month><Day>07</Day></DateCompleted><DateRevised><Year>2020</Year><Month>04</Month><Day>01</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">2211-1247</ISSN><JournalIssue CitedMedium="Internet"><Volume>24</Volume><Issue>2</Issue><PubDate><Year>2018</Year><Month>07</Month><Day>10</Day></PubDate></JournalIssue><Title>Cell reports</Title><ISOAbbreviation>Cell Rep</ISOAbbreviation></Journal><ArticleTitle>Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein.</ArticleTitle><Pagination><MedlinePgn>441-452</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S2211-1247(18)30951-3</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.celrep.2018.06.041</ELocationID><Abstract><AbstractText>The major mechanism of antibody-mediated neutralization of the Middle East respiratory syndrome coronavirus (MERS-CoV) involves competition with the cellular receptor dipeptidyl peptidase 4 (DPP4) for binding to the receptor-binding domain (RBD) of the spike (S) glycoprotein. Here, we report a unique epitope and unusual neutralizing mechanism of the isolated human antibody MERS-4. Structurally, MERS-4 approached the RBD from the outside of the RBD-DPP4 binding interface. Such binding resulted in the folding of the β5-β6 loop toward a shallow groove on the RBD interface critical for accommodating DPP4. The key residues for binding are identified through site-directed mutagenesis. Structural modeling revealed that MERS-4 binds to RBD only in the "up" position in the S trimer. Furthermore, MERS-4 demonstrated synergy with several reported antibodies. These results indicate that MERS-4 neutralizes MERS-CoV by indirect rather than direct competition with DPP4. This mechanism provides a valuable addition for the combined use of antibodies against MERS-CoV infection.</AbstractText><CopyrightInformation>Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Senyan</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhou</LastName><ForeName>Panpan</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Pengfei</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Yangyang</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jiang</LastName><ForeName>Liwei</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jia</LastName><ForeName>Wenxu</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Han</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fan</LastName><ForeName>Angela</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Dongli</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shi</LastName><ForeName>Xuanling</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fang</LastName><ForeName>Xianyang</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hammel</LastName><ForeName>Michal</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Shuying</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan 701, Taiwan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Xinquan</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China; Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. Electronic address: xinquanwang@mail.tsinghua.edu.cn.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Linqi</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China. Electronic address: zhanglinqi@mail.tsinghua.edu.cn.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Cell Rep</MedlineTA><NlmUniqueID>101573691</NlmUniqueID></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D057134">Antibodies, Neutralizing</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000939">Epitopes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D064370">Spike Glycoprotein, Coronavirus</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D057134" MajorTopicYN="N">Antibodies, Neutralizing</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001665" MajorTopicYN="N">Binding Sites</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000939" MajorTopicYN="N">Epitopes</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D065207" MajorTopicYN="N">Middle East Respiratory Syndrome Coronavirus</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008958" MajorTopicYN="N">Models, Molecular</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009154" MajorTopicYN="N">Mutation</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011485" MajorTopicYN="N">Protein Binding</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000072417" MajorTopicYN="N">Protein Domains</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055503" MajorTopicYN="N">Protein Multimerization</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D064370" MajorTopicYN="N">Spike Glycoprotein, Coronavirus</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Middle East respiratory syndrome</Keyword><Keyword MajorTopicYN="Y">antibody epitope</Keyword><Keyword MajorTopicYN="Y">coronavirus</Keyword><Keyword MajorTopicYN="Y">crystal structure</Keyword><Keyword MajorTopicYN="Y">neutralizing antibody</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate 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