Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27
Identifieur interne : 001564 ( Main/Exploration ); précédent : 001563; suivant : 001565Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27
Auteurs : Xiaojuan Yu [République populaire de Chine] ; Senyan Zhang [République populaire de Chine] ; Liwei Jiang [République populaire de Chine] ; Ye Cui [République populaire de Chine] ; Dongxia Li ; Dongli Wang [République populaire de Chine] ; Nianshuang Wang [République populaire de Chine] ; Lili Fu [République populaire de Chine] ; Xuanlin Shi [République populaire de Chine] ; Ziqiang Li ; Linqi Zhang [République populaire de Chine] ; Xinquan Wang [République populaire de Chine]Source :
- Scientific Reports [ 2045-2322 ] ; 2015.
Descripteurs français
- KwdFr :
- Anticorps monoclonaux (), Anticorps monoclonaux (ultrastructure), Antiviraux (), Coronavirus du syndrome respiratoire du Moyen-Orient (), Coronavirus du syndrome respiratoire du Moyen-Orient (ultrastructure), Humains, Liaison aux protéines, Modèles chimiques, Protéines de l'enveloppe virale (), Protéines de l'enveloppe virale (ultrastructure), Relation structure-activité, Simulation de docking moléculaire, Sites de fixation.
- MESH :
English descriptors
- KwdEn :
- Antibodies, Monoclonal (chemistry), Antibodies, Monoclonal (ultrastructure), Antiviral Agents (chemistry), Binding Sites, Humans, Middle East Respiratory Syndrome Coronavirus (chemistry), Middle East Respiratory Syndrome Coronavirus (ultrastructure), Models, Chemical, Molecular Docking Simulation, Protein Binding, Structure-Activity Relationship, Viral Envelope Proteins (chemistry), Viral Envelope Proteins (ultrastructure).
- MESH :
- chemical , chemistry : Antibodies, Monoclonal, Antiviral Agents, Viral Envelope Proteins.
- chemical , ultrastructure : Antibodies, Monoclonal, Viral Envelope Proteins.
- chemistry : Middle East Respiratory Syndrome Coronavirus.
- ultrastructure : Middle East Respiratory Syndrome Coronavirus.
- Binding Sites, Humans, Models, Chemical, Molecular Docking Simulation, Protein Binding, Structure-Activity Relationship.
Abstract
The recently reported Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans with an approximately 30% mortality rate. The envelope spike glycoprotein on the surface of MERS-CoV mediates receptor binding, membrane fusion and viral entry. We previously reported two human monoclonal antibodies that target the receptor binding domain (RBD) of the spike and exhibit strong neutralization activity against live and pesudotyped MERS-CoV infection. Here we determined the crystal structure of MERS-CoV RBD bound to the Fab fragment of MERS-27 antibody at 3.20 Å resolution. The MERS-27 epitope in the RBD overlaps with the binding site of the MERS-CoV receptor DPP4. Further biochemical, viral entry and neutralization analyses identified two critical residues in the RBD for both MERS-27 recognition and DPP4 binding. One of the residues, Trp535, was found to function as an anchor residue at the binding interface with MERS-27. Upon receptor binding, Trp535 interacts with the N-linked carbohydrate moiety of DPP4. Thus, MERS-27 inhibits MERS-CoV infection by directly blocking both protein-protein and protein-carbohydrate interactions between MERS-CoV RBD and DPP4. These results shed light on the molecular basis of MERS-27 neutralization and will assist in the optimization of MERS-27 as a tool to combat MERS-CoV infection.
The online version of this article (doi:10.1038/srep13133) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1038/srep13133
PubMed: 26281793
PubMed Central: 4539535
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000425
- to stream Pmc, to step Curation: 000425
- to stream Pmc, to step Checkpoint: 000D18
- to stream PubMed, to step Corpus: 001504
- to stream PubMed, to step Curation: 001504
- to stream PubMed, to step Checkpoint: 001335
- to stream Ncbi, to step Merge: 001234
- to stream Ncbi, to step Curation: 001234
- to stream Ncbi, to step Checkpoint: 001234
- to stream Main, to step Merge: 001569
- to stream Main, to step Curation: 001564
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27</title><author><name sortKey="Yu, Xiaojuan" sort="Yu, Xiaojuan" uniqKey="Yu X" first="Xiaojuan" last="Yu">Xiaojuan Yu</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution>Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Collaborative Innovation Center for Biotherapy, Tsinghua University,</institution></institution-wrap>Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Senyan" sort="Zhang, Senyan" uniqKey="Zhang S" first="Senyan" last="Zhang">Senyan Zhang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution>Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Collaborative Innovation Center for Biotherapy, Tsinghua University,</institution></institution-wrap>Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</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:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University,</institution></institution-wrap>Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Cui, Ye" sort="Cui, Ye" uniqKey="Cui Y" first="Ye" last="Cui">Ye Cui</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution>Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Collaborative Innovation Center for Biotherapy, Tsinghua University,</institution></institution-wrap>Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Li, Dongxia" sort="Li, Dongxia" uniqKey="Li D" first="Dongxia" last="Li">Dongxia Li</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.460117.5</institution-id><institution>Beijing VDJBio Co., Ltd, Suite B311, 5 Kaituo Road, Zhongguancun BioMedical Garden,</institution></institution-wrap>Haidian District, Beijing China</nlm:aff><wicri:noCountry code="subfield">Beijing China</wicri:noCountry></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:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution>Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Collaborative Innovation Center for Biotherapy, Tsinghua University,</institution></institution-wrap>Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Nianshuang" sort="Wang, Nianshuang" uniqKey="Wang N" first="Nianshuang" last="Wang">Nianshuang Wang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution>Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Collaborative Innovation Center for Biotherapy, Tsinghua University,</institution></institution-wrap>Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Fu, Lili" sort="Fu, Lili" uniqKey="Fu L" first="Lili" last="Fu">Lili Fu</name><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University,</institution></institution-wrap>Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Shi, Xuanlin" sort="Shi, Xuanlin" uniqKey="Shi X" first="Xuanlin" last="Shi">Xuanlin Shi</name><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University,</institution></institution-wrap>Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Li, Ziqiang" sort="Li, Ziqiang" uniqKey="Li Z" first="Ziqiang" last="Li">Ziqiang Li</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.460117.5</institution-id><institution>Beijing VDJBio Co., Ltd, Suite B311, 5 Kaituo Road, Zhongguancun BioMedical Garden,</institution></institution-wrap>Haidian District, Beijing China</nlm:aff><wicri:noCountry code="subfield">Beijing China</wicri:noCountry></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:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University,</institution></institution-wrap>Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</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:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution>Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Collaborative Innovation Center for Biotherapy, Tsinghua University,</institution></institution-wrap>Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff4">Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>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><wicri:noRegion>Chengdu</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26281793</idno><idno type="pmc">4539535</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539535</idno><idno type="RBID">PMC:4539535</idno><idno type="doi">10.1038/srep13133</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000425</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000425</idno><idno type="wicri:Area/Pmc/Curation">000425</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000425</idno><idno type="wicri:Area/Pmc/Checkpoint">000D18</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000D18</idno><idno type="wicri:source">PubMed</idno><idno type="RBID">pubmed:26281793</idno><idno type="wicri:Area/PubMed/Corpus">001504</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001504</idno><idno type="wicri:Area/PubMed/Curation">001504</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001504</idno><idno type="wicri:Area/PubMed/Checkpoint">001335</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001335</idno><idno type="wicri:Area/Ncbi/Merge">001234</idno><idno type="wicri:Area/Ncbi/Curation">001234</idno><idno type="wicri:Area/Ncbi/Checkpoint">001234</idno><idno type="wicri:Area/Main/Merge">001569</idno><idno type="wicri:Area/Main/Curation">001564</idno><idno type="wicri:Area/Main/Exploration">001564</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27</title><author><name sortKey="Yu, Xiaojuan" sort="Yu, Xiaojuan" uniqKey="Yu X" first="Xiaojuan" last="Yu">Xiaojuan Yu</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution>Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Collaborative Innovation Center for Biotherapy, Tsinghua University,</institution></institution-wrap>Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Senyan" sort="Zhang, Senyan" uniqKey="Zhang S" first="Senyan" last="Zhang">Senyan Zhang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution>Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Collaborative Innovation Center for Biotherapy, Tsinghua University,</institution></institution-wrap>Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</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:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University,</institution></institution-wrap>Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Cui, Ye" sort="Cui, Ye" uniqKey="Cui Y" first="Ye" last="Cui">Ye Cui</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution>Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Collaborative Innovation Center for Biotherapy, Tsinghua University,</institution></institution-wrap>Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Li, Dongxia" sort="Li, Dongxia" uniqKey="Li D" first="Dongxia" last="Li">Dongxia Li</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.460117.5</institution-id><institution>Beijing VDJBio Co., Ltd, Suite B311, 5 Kaituo Road, Zhongguancun BioMedical Garden,</institution></institution-wrap>Haidian District, Beijing China</nlm:aff><wicri:noCountry code="subfield">Beijing China</wicri:noCountry></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:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution>Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Collaborative Innovation Center for Biotherapy, Tsinghua University,</institution></institution-wrap>Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Nianshuang" sort="Wang, Nianshuang" uniqKey="Wang N" first="Nianshuang" last="Wang">Nianshuang Wang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution>Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Collaborative Innovation Center for Biotherapy, Tsinghua University,</institution></institution-wrap>Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Fu, Lili" sort="Fu, Lili" uniqKey="Fu L" first="Lili" last="Fu">Lili Fu</name><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University,</institution></institution-wrap>Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Shi, Xuanlin" sort="Shi, Xuanlin" uniqKey="Shi X" first="Xuanlin" last="Shi">Xuanlin Shi</name><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University,</institution></institution-wrap>Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Li, Ziqiang" sort="Li, Ziqiang" uniqKey="Li Z" first="Ziqiang" last="Li">Ziqiang Li</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.460117.5</institution-id><institution>Beijing VDJBio Co., Ltd, Suite B311, 5 Kaituo Road, Zhongguancun BioMedical Garden,</institution></institution-wrap>Haidian District, Beijing China</nlm:aff><wicri:noCountry code="subfield">Beijing China</wicri:noCountry></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:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University,</institution></institution-wrap>Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</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:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution>Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Collaborative Innovation Center for Biotherapy, Tsinghua University,</institution></institution-wrap>Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff4">Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>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><wicri:noRegion>Chengdu</wicri:noRegion></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antibodies, Monoclonal (chemistry)</term><term>Antibodies, Monoclonal (ultrastructure)</term><term>Antiviral Agents (chemistry)</term><term>Binding Sites</term><term>Humans</term><term>Middle East Respiratory Syndrome Coronavirus (chemistry)</term><term>Middle East Respiratory Syndrome Coronavirus (ultrastructure)</term><term>Models, Chemical</term><term>Molecular Docking Simulation</term><term>Protein Binding</term><term>Structure-Activity Relationship</term><term>Viral Envelope Proteins (chemistry)</term><term>Viral Envelope Proteins (ultrastructure)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Anticorps monoclonaux ()</term><term>Anticorps monoclonaux (ultrastructure)</term><term>Antiviraux ()</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient ()</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (ultrastructure)</term><term>Humains</term><term>Liaison aux protéines</term><term>Modèles chimiques</term><term>Protéines de l'enveloppe virale ()</term><term>Protéines de l'enveloppe virale (ultrastructure)</term><term>Relation structure-activité</term><term>Simulation de docking moléculaire</term><term>Sites de fixation</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Antiviral Agents</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="ultrastructure" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="ultrastructure" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Binding Sites</term><term>Humans</term><term>Models, Chemical</term><term>Molecular Docking Simulation</term><term>Protein Binding</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Anticorps monoclonaux</term><term>Antiviraux</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Humains</term><term>Liaison aux protéines</term><term>Modèles chimiques</term><term>Protéines de l'enveloppe virale</term><term>Relation structure-activité</term><term>Simulation de docking moléculaire</term><term>Sites de fixation</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The recently reported Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans with an approximately 30% mortality rate. The envelope spike glycoprotein on the surface of MERS-CoV mediates receptor binding, membrane fusion and viral entry. We previously reported two human monoclonal antibodies that target the receptor binding domain (RBD) of the spike and exhibit strong neutralization activity against live and pesudotyped MERS-CoV infection. Here we determined the crystal structure of MERS-CoV RBD bound to the Fab fragment of MERS-27 antibody at 3.20 Å resolution. The MERS-27 epitope in the RBD overlaps with the binding site of the MERS-CoV receptor DPP4. Further biochemical, viral entry and neutralization analyses identified two critical residues in the RBD for both MERS-27 recognition and DPP4 binding. One of the residues, Trp535, was found to function as an anchor residue at the binding interface with MERS-27. Upon receptor binding, Trp535 interacts with the N-linked carbohydrate moiety of DPP4. Thus, MERS-27 inhibits MERS-CoV infection by directly blocking both protein-protein and protein-carbohydrate interactions between MERS-CoV RBD and DPP4. These results shed light on the molecular basis of MERS-27 neutralization and will assist in the optimization of MERS-27 as a tool to combat MERS-CoV infection.</p><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1038/srep13133) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zaki, Am" uniqKey="Zaki A">AM Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S van Boheemen</name></author><author><name sortKey="Bestebroer, Tm" uniqKey="Bestebroer T">TM Bestebroer</name></author><author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name></author><author><name sortKey="Fouchier, Ra" uniqKey="Fouchier R">RA Fouchier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Groot, Rj" uniqKey="De Groot R">RJ de Groot</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Bermingham, A" uniqKey="Bermingham A">A Bermingham</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author><author><name sortKey="Zumla, Ai" uniqKey="Zumla A">AI Zumla</name></author><author><name sortKey="Al Hakeem, Rf" uniqKey="Al Hakeem R">RF Al-Hakeem</name></author><author><name sortKey="Al Rabeeah, Aa" uniqKey="Al Rabeeah A">AA Al-Rabeeah</name></author><author><name sortKey="Stephens, Gm" uniqKey="Stephens G">GM Stephens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Assiri, A" uniqKey="Assiri A">A Assiri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hijawi, B" uniqKey="Hijawi B">B Hijawi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Assiri, A" uniqKey="Assiri A">A Assiri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guery, B" uniqKey="Guery B">B Guery</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Woo, Pcy" uniqKey="Woo P">PCY Woo</name></author><author><name sortKey="Lau, Skp" uniqKey="Lau S">SKP Lau</name></author><author><name sortKey="Li, Ksm" uniqKey="Li K">KSM Li</name></author><author><name sortKey="Tsang, Akl" uniqKey="Tsang A">AKL Tsang</name></author><author><name sortKey="Yuen, K Y" uniqKey="Yuen K">K-Y Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S van Boheemen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ithete, Nl" uniqKey="Ithete N">NL Ithete</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reusken, Cb" uniqKey="Reusken C">CB Reusken</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hemida, Mg" uniqKey="Hemida M">MG Hemida</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Haagmans, Bl" uniqKey="Haagmans B">BL Haagmans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Peiris, Jsm" uniqKey="Peiris J">JSM Peiris</name></author><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y Guan</name></author><author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cauchemez, S" uniqKey="Cauchemez S">S Cauchemez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Breban, R" uniqKey="Breban R">R Breban</name></author><author><name sortKey="Riou, J" uniqKey="Riou J">J Riou</name></author><author><name sortKey="Fontanet, A" uniqKey="Fontanet A">A Fontanet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Masters, Ps" uniqKey="Masters P">PS Masters</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Raj, Vs" uniqKey="Raj V">VS Raj</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jiang, S" uniqKey="Jiang S">S Jiang</name></author><author><name sortKey="Lu, L" uniqKey="Lu L">L Lu</name></author><author><name sortKey="Du, L" uniqKey="Du L">L Du</name></author><author><name sortKey="Debnath, Ak" uniqKey="Debnath A">AK Debnath</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mou, H" uniqKey="Mou H">H Mou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, N" uniqKey="Wang N">N Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, G" uniqKey="Lu G">G Lu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jiang, L" uniqKey="Jiang L">L Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tang, Xc" uniqKey="Tang X">XC Tang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ying, T" uniqKey="Ying T">T Ying</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Du, L" uniqKey="Du L">L Du</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Otwinowski, Z" uniqKey="Otwinowski Z">Z Otwinowski</name></author><author><name sortKey="Minor, W" uniqKey="Minor W">W Minor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mccoy, Aj" uniqKey="Mccoy A">AJ McCoy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Adams, Pd" uniqKey="Adams P">PD Adams</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Emsley, P" uniqKey="Emsley P">P Emsley</name></author><author><name sortKey="Cowtan, K" uniqKey="Cowtan K">K Cowtan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Laskowski, Ra" uniqKey="Laskowski R">RA Laskowski</name></author><author><name sortKey="Macarthur, Mw" uniqKey="Macarthur M">MW MacArthur</name></author><author><name sortKey="Moss, Ds" uniqKey="Moss D">DS Moss</name></author><author><name sortKey="Thornton, Jm" uniqKey="Thornton J">JM Thornton</name></author></analytic></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><noCountry><name sortKey="Li, Dongxia" sort="Li, Dongxia" uniqKey="Li D" first="Dongxia" last="Li">Dongxia Li</name><name sortKey="Li, Ziqiang" sort="Li, Ziqiang" uniqKey="Li Z" first="Ziqiang" last="Li">Ziqiang Li</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Yu, Xiaojuan" sort="Yu, Xiaojuan" uniqKey="Yu X" first="Xiaojuan" last="Yu">Xiaojuan Yu</name></noRegion><name sortKey="Cui, Ye" sort="Cui, Ye" uniqKey="Cui Y" first="Ye" last="Cui">Ye Cui</name><name sortKey="Fu, Lili" sort="Fu, Lili" uniqKey="Fu L" first="Lili" last="Fu">Lili Fu</name><name sortKey="Jiang, Liwei" sort="Jiang, Liwei" uniqKey="Jiang L" first="Liwei" last="Jiang">Liwei Jiang</name><name sortKey="Shi, Xuanlin" sort="Shi, Xuanlin" uniqKey="Shi X" first="Xuanlin" last="Shi">Xuanlin Shi</name><name sortKey="Wang, Dongli" sort="Wang, Dongli" uniqKey="Wang D" first="Dongli" last="Wang">Dongli Wang</name><name sortKey="Wang, Nianshuang" sort="Wang, Nianshuang" uniqKey="Wang N" first="Nianshuang" last="Wang">Nianshuang Wang</name><name sortKey="Wang, Xinquan" sort="Wang, Xinquan" uniqKey="Wang X" first="Xinquan" last="Wang">Xinquan Wang</name><name sortKey="Wang, Xinquan" sort="Wang, Xinquan" uniqKey="Wang X" first="Xinquan" last="Wang">Xinquan Wang</name><name sortKey="Zhang, Linqi" sort="Zhang, Linqi" uniqKey="Zhang L" first="Linqi" last="Zhang">Linqi Zhang</name><name sortKey="Zhang, Senyan" sort="Zhang, Senyan" uniqKey="Zhang S" first="Senyan" last="Zhang">Senyan Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001564 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001564 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= MersV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= PMC:4539535
|texte= Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:26281793" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a MersV1
| This area was generated with Dilib version V0.6.33. |  |