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Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains

Identifieur interne : 000E58 ( Main/Exploration ); précédent : 000E57; suivant : 000E59

Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains

Auteurs : Yuan Yuan [République populaire de Chine] ; Duanfang Cao [République populaire de Chine] ; Yanfang Zhang [République populaire de Chine] ; Jun Ma [République populaire de Chine] ; Jianxun Qi [République populaire de Chine] ; Qihui Wang [République populaire de Chine] ; Guangwen Lu ; Ying Wu [République populaire de Chine] ; Jinghua Yan [République populaire de Chine] ; Yi Shi [République populaire de Chine] ; Xinzheng Zhang [République populaire de Chine] ; George F. Gao [République populaire de Chine]

Source :

RBID : PMC:5394239

Descripteurs français

English descriptors

Abstract

The envelope spike (S) proteins of MERS-CoV and SARS-CoV determine the virus host tropism and entry into host cells, and constitute a promising target for the development of prophylactics and therapeutics. Here, we present high-resolution structures of the trimeric MERS-CoV and SARS-CoV S proteins in its pre-fusion conformation by single particle cryo-electron microscopy. The overall structures resemble that from other coronaviruses including HKU1, MHV and NL63 reported recently, with the exception of the receptor binding domain (RBD). We captured two states of the RBD with receptor binding region either buried (lying state) or exposed (standing state), demonstrating an inherently flexible RBD readily recognized by the receptor. Further sequence conservation analysis of six human-infecting coronaviruses revealed that the fusion peptide, HR1 region and the central helix are potential targets for eliciting broadly neutralizing antibodies.

Supplementary information

The online version of this article (doi:10.1038/ncomms15092) contains supplementary material, which is available to authorized users.


Url:
DOI: 10.1038/ncomms15092
PubMed: 28393837
PubMed Central: 5394239


Affiliations:


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Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<author>
<name sortKey="Qi, Jianxun" sort="Qi, Jianxun" uniqKey="Qi J" first="Jianxun" last="Qi">Jianxun Qi</name>
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Beijing, 100101 China</nlm:aff>
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<name sortKey="Wang, Qihui" sort="Wang, Qihui" uniqKey="Wang Q" first="Qihui" last="Wang">Qihui Wang</name>
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Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
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<author>
<name sortKey="Lu, Guangwen" sort="Lu, Guangwen" uniqKey="Lu G" first="Guangwen" last="Lu">Guangwen Lu</name>
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<nlm:aff id="Aff6">West China Hospital Emergency Department (WCHED), State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, 610041 Sichuan China</nlm:aff>
<wicri:noCountry code="subfield">610041 Sichuan China</wicri:noCountry>
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<name sortKey="Wu, Ying" sort="Wu, Ying" uniqKey="Wu Y" first="Ying" last="Wu">Ying Wu</name>
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<institution-id institution-id-type="GRID">grid.49470.3e</institution-id>
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<institution>School of Basic Medical Sciences, Wuhan University,</institution>
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Wuhan, 430071 China</nlm:aff>
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<wicri:regionArea>Wuhan</wicri:regionArea>
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<author>
<name sortKey="Yan, Jinghua" sort="Yan, Jinghua" uniqKey="Yan J" first="Jinghua" last="Yan">Jinghua Yan</name>
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Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
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<nlm:aff id="Aff8">
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<institution>Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital,</institution>
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Shenzhen, 518112 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Shenzhen</wicri:regionArea>
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<institution>Center for Influenza Research and Early-warning, Chinese Academy of Sciences (CASCIRE),</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
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<institution>Medical School, University of Chinese Academy of Sciences,</institution>
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Beijing, 101408 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
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</author>
<author>
<name sortKey="Shi, Yi" sort="Shi, Yi" uniqKey="Shi Y" first="Yi" last="Shi">Yi Shi</name>
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</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="Aff8">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.410741.7</institution-id>
<institution>Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital,</institution>
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Shenzhen, 518112 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Shenzhen</wicri:regionArea>
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<nlm:aff id="Aff9">
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<institution-id institution-id-type="GRID">grid.9227.e</institution-id>
<institution-id institution-id-type="ISNI">0000000119573309</institution-id>
<institution>Center for Influenza Research and Early-warning, Chinese Academy of Sciences (CASCIRE),</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="Aff10">
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<institution-id institution-id-type="ISNI">0000 0004 1797 8419</institution-id>
<institution>Medical School, University of Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 101408 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
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</author>
<author>
<name sortKey="Zhang, Xinzheng" sort="Zhang, Xinzheng" uniqKey="Zhang X" first="Xinzheng" last="Zhang">Xinzheng Zhang</name>
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<institution-wrap>
<institution-id institution-id-type="GRID">grid.418856.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1792 5640</institution-id>
<institution>National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
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<affiliation wicri:level="1">
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<institution-wrap>
<institution-id institution-id-type="GRID">grid.418856.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1792 5640</institution-id>
<institution>Center for Biological Imaging, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name>
<affiliation>
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.59053.3a</institution-id>
<institution-id institution-id-type="ISNI">0000000121679639</institution-id>
<institution>School of Life Sciences, University of Science and Technology of China,</institution>
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Hefei, 230026 Anhui China</nlm:aff>
<wicri:noCountry code="subfield">230026 Anhui China</wicri:noCountry>
</affiliation>
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<nlm:aff id="Aff2">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
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</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="Aff4">Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Biotechnology, Tianjin, 300308 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Biotechnology, Tianjin</wicri:regionArea>
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<settlement type="city">Tianjin</settlement>
</placeName>
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<institution>Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital,</institution>
</institution-wrap>
Shenzhen, 518112 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Shenzhen</wicri:regionArea>
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<nlm:aff id="Aff9">
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<institution-id institution-id-type="GRID">grid.9227.e</institution-id>
<institution-id institution-id-type="ISNI">0000000119573309</institution-id>
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</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
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<institution-id institution-id-type="ISNI">0000 0004 1797 8419</institution-id>
<institution>Medical School, University of Chinese Academy of Sciences,</institution>
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Beijing, 101408 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
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<affiliation wicri:level="1">
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<institution-id institution-id-type="GRID">grid.198530.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0000 8803 2373</institution-id>
<institution>National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC),</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
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</analytic>
<series>
<title level="j">Nature Communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint>
<date when="2017">2017</date>
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<keywords scheme="KwdEn" xml:lang="en">
<term>Antibodies, Neutralizing</term>
<term>Antiviral Agents (pharmacology)</term>
<term>Cryoelectron Microscopy</term>
<term>Glycoproteins (chemistry)</term>
<term>Glycoproteins (ultrastructure)</term>
<term>Glycosylation</term>
<term>Membrane Fusion (drug effects)</term>
<term>Middle East Respiratory Syndrome Coronavirus (ultrastructure)</term>
<term>Models, Molecular</term>
<term>Protein Binding</term>
<term>Protein Domains</term>
<term>Protein Multimerization</term>
<term>Receptors, Virus (metabolism)</term>
<term>SARS Virus (ultrastructure)</term>
<term>Spike Glycoprotein, Coronavirus (chemistry)</term>
<term>Spike Glycoprotein, Coronavirus (ultrastructure)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Anticorps neutralisants</term>
<term>Antiviraux (pharmacologie)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (ultrastructure)</term>
<term>Cryomicroscopie électronique</term>
<term>Domaines protéiques</term>
<term>Fusion membranaire ()</term>
<term>Glycoprotéine de spicule des coronavirus ()</term>
<term>Glycoprotéine de spicule des coronavirus (ultrastructure)</term>
<term>Glycoprotéines ()</term>
<term>Glycoprotéines (ultrastructure)</term>
<term>Glycosylation</term>
<term>Liaison aux protéines</term>
<term>Modèles moléculaires</term>
<term>Multimérisation de protéines</term>
<term>Récepteurs viraux (métabolisme)</term>
<term>Virus du SRAS (ultrastructure)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en">
<term>Glycoproteins</term>
<term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Receptors, Virus</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en">
<term>Antiviral Agents</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="ultrastructure" xml:lang="en">
<term>Glycoproteins</term>
<term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" type="chemical" xml:lang="en">
<term>Antibodies, Neutralizing</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en">
<term>Membrane Fusion</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Récepteurs viraux</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr">
<term>Antiviraux</term>
</keywords>
<keywords scheme="MESH" qualifier="ultrastructure" xml:lang="en">
<term>Middle East Respiratory Syndrome Coronavirus</term>
<term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Cryoelectron Microscopy</term>
<term>Glycosylation</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>Anticorps neutralisants</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Cryomicroscopie électronique</term>
<term>Domaines protéiques</term>
<term>Fusion membranaire</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines</term>
<term>Glycosylation</term>
<term>Liaison aux protéines</term>
<term>Modèles moléculaires</term>
<term>Multimérisation de protéines</term>
<term>Virus du SRAS</term>
</keywords>
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<front>
<div type="abstract" xml:lang="en">
<p id="Par1">The envelope spike (S) proteins of MERS-CoV and SARS-CoV determine the virus host tropism and entry into host cells, and constitute a promising target for the development of prophylactics and therapeutics. Here, we present high-resolution structures of the trimeric MERS-CoV and SARS-CoV S proteins in its pre-fusion conformation by single particle cryo-electron microscopy. The overall structures resemble that from other coronaviruses including HKU1, MHV and NL63 reported recently, with the exception of the receptor binding domain (RBD). We captured two states of the RBD with receptor binding region either buried (lying state) or exposed (standing state), demonstrating an inherently flexible RBD readily recognized by the receptor. Further sequence conservation analysis of six human-infecting coronaviruses revealed that the fusion peptide, HR1 region and the central helix are potential targets for eliciting broadly neutralizing antibodies.</p>
<sec>
<title>Supplementary information</title>
<p>The online version of this article (doi:10.1038/ncomms15092) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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<name sortKey="Shi, Yi" sort="Shi, Yi" uniqKey="Shi Y" first="Yi" last="Shi">Yi Shi</name>
<name sortKey="Shi, Yi" sort="Shi, Yi" uniqKey="Shi Y" first="Yi" last="Shi">Yi Shi</name>
<name sortKey="Wang, Qihui" sort="Wang, Qihui" uniqKey="Wang Q" first="Qihui" last="Wang">Qihui Wang</name>
<name sortKey="Wu, Ying" sort="Wu, Ying" uniqKey="Wu Y" first="Ying" last="Wu">Ying Wu</name>
<name sortKey="Yan, Jinghua" sort="Yan, Jinghua" uniqKey="Yan J" first="Jinghua" last="Yan">Jinghua Yan</name>
<name sortKey="Yan, Jinghua" sort="Yan, Jinghua" uniqKey="Yan J" first="Jinghua" last="Yan">Jinghua Yan</name>
<name sortKey="Yan, Jinghua" sort="Yan, Jinghua" uniqKey="Yan J" first="Jinghua" last="Yan">Jinghua Yan</name>
<name sortKey="Yan, Jinghua" sort="Yan, Jinghua" uniqKey="Yan J" first="Jinghua" last="Yan">Jinghua Yan</name>
<name sortKey="Zhang, Xinzheng" sort="Zhang, Xinzheng" uniqKey="Zhang X" first="Xinzheng" last="Zhang">Xinzheng Zhang</name>
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<name sortKey="Zhang, Yanfang" sort="Zhang, Yanfang" uniqKey="Zhang Y" first="Yanfang" last="Zhang">Yanfang Zhang</name>
<name sortKey="Zhang, Yanfang" sort="Zhang, Yanfang" uniqKey="Zhang Y" first="Yanfang" last="Zhang">Yanfang Zhang</name>
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</record>

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