Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2.
Identifieur interne : 000171 ( PubMed/Checkpoint ); précédent : 000170; suivant : 000172Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2.
Auteurs : Qihui Wang [République populaire de Chine] ; Yanfang Zhang [République populaire de Chine] ; Lili Wu [République populaire de Chine] ; Sheng Niu [République populaire de Chine] ; Chunli Song [République populaire de Chine] ; Zengyuan Zhang [République populaire de Chine] ; Guangwen Lu [République populaire de Chine] ; Chengpeng Qiao [République populaire de Chine] ; Yu Hu [République populaire de Chine] ; Kwok-Yung Yuen [République populaire de Chine] ; Qisheng Wang [République populaire de Chine] ; Huan Zhou [République populaire de Chine] ; Jinghua Yan [République populaire de Chine] ; Jianxun Qi [République populaire de Chine]Source :
- Cell [ 1097-4172 ] ; 2020.
Abstract
The recent emergence of a novel coronavirus (SARS-CoV-2) in China has caused significant public health concerns. Recently, ACE2 was reported as an entry receptor for SARS-CoV-2. In this study, we present the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in complex with human ACE2 (hACE2), which reveals a hACE2-binding mode similar overall to that observed for SARS-CoV. However, atomic details at the binding interface demonstrate that key residue substitutions in SARS-CoV-2-CTD slightly strengthen the interaction and lead to higher affinity for receptor binding than SARS-RBD. Additionally, a panel of murine monoclonal antibodies (mAbs) and polyclonal antibodies (pAbs) against SARS-CoV-S1/receptor-binding domain (RBD) were unable to interact with the SARS-CoV-2 S protein, indicating notable differences in antigenicity between SARS-CoV and SARS-CoV-2. These findings shed light on the viral pathogenesis and provide important structural information regarding development of therapeutic countermeasures against the emerging virus.
DOI: 10.1016/j.cell.2020.03.045
PubMed: 32275855
Affiliations:
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<front><div type="abstract" xml:lang="en">The recent emergence of a novel coronavirus (SARS-CoV-2) in China has caused significant public health concerns. Recently, ACE2 was reported as an entry receptor for SARS-CoV-2. In this study, we present the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in complex with human ACE2 (hACE2), which reveals a hACE2-binding mode similar overall to that observed for SARS-CoV. However, atomic details at the binding interface demonstrate that key residue substitutions in SARS-CoV-2-CTD slightly strengthen the interaction and lead to higher affinity for receptor binding than SARS-RBD. Additionally, a panel of murine monoclonal antibodies (mAbs) and polyclonal antibodies (pAbs) against SARS-CoV-S1/receptor-binding domain (RBD) were unable to interact with the SARS-CoV-2 S protein, indicating notable differences in antigenicity between SARS-CoV and SARS-CoV-2. These findings shed light on the viral pathogenesis and provide important structural information regarding development of therapeutic countermeasures against the emerging virus.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">32275855</PMID>
<DateRevised><Year>2020</Year>
<Month>04</Month>
<Day>13</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1097-4172</ISSN>
<JournalIssue CitedMedium="Internet"><PubDate><Year>2020</Year>
<Month>Apr</Month>
<Day>07</Day>
</PubDate>
</JournalIssue>
<Title>Cell</Title>
<ISOAbbreviation>Cell</ISOAbbreviation>
</Journal>
<ArticleTitle>Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2.</ArticleTitle>
<ELocationID EIdType="pii" ValidYN="Y">S0092-8674(20)30338-X</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.cell.2020.03.045</ELocationID>
<Abstract><AbstractText>The recent emergence of a novel coronavirus (SARS-CoV-2) in China has caused significant public health concerns. Recently, ACE2 was reported as an entry receptor for SARS-CoV-2. In this study, we present the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in complex with human ACE2 (hACE2), which reveals a hACE2-binding mode similar overall to that observed for SARS-CoV. However, atomic details at the binding interface demonstrate that key residue substitutions in SARS-CoV-2-CTD slightly strengthen the interaction and lead to higher affinity for receptor binding than SARS-RBD. Additionally, a panel of murine monoclonal antibodies (mAbs) and polyclonal antibodies (pAbs) against SARS-CoV-S1/receptor-binding domain (RBD) were unable to interact with the SARS-CoV-2 S protein, indicating notable differences in antigenicity between SARS-CoV and SARS-CoV-2. These findings shed light on the viral pathogenesis and provide important structural information regarding development of therapeutic countermeasures against the emerging virus.</AbstractText>
<CopyrightInformation>Copyright © 2020 Elsevier Inc. All rights reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wang</LastName>
<ForeName>Qihui</ForeName>
<Initials>Q</Initials>
<AffiliationInfo><Affiliation>CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zhang</LastName>
<ForeName>Yanfang</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China; Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Biotechnology, Tianjin 300308, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wu</LastName>
<ForeName>Lili</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Niu</LastName>
<ForeName>Sheng</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Song</LastName>
<ForeName>Chunli</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Institute of Physical Science and Information, Anhui University, Hefei 230039, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zhang</LastName>
<ForeName>Zengyuan</ForeName>
<Initials>Z</Initials>
<AffiliationInfo><Affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lu</LastName>
<ForeName>Guangwen</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>West China Hospital Emergency Department (WCHED), State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Qiao</LastName>
<ForeName>Chengpeng</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hu</LastName>
<ForeName>Yu</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Yuen</LastName>
<ForeName>Kwok-Yung</ForeName>
<Initials>KY</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China; Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wang</LastName>
<ForeName>Qisheng</ForeName>
<Initials>Q</Initials>
<AffiliationInfo><Affiliation>Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201204, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zhou</LastName>
<ForeName>Huan</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201204, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Yan</LastName>
<ForeName>Jinghua</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Institute of Physical Science and Information, Anhui University, Hefei 230039, China; College of Life Science, University of the Chinese Academy of Sciences, Beijing 100049, China. Electronic address: yanjh@im.ac.cn.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Qi</LastName>
<ForeName>Jianxun</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of the Chinese Academy of Sciences, Beijing 100049, China. Electronic address: jxqi@im.ac.cn.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2020</Year>
<Month>04</Month>
<Day>07</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Cell</MedlineTA>
<NlmUniqueID>0413066</NlmUniqueID>
<ISSNLinking>0092-8674</ISSNLinking>
</MedlineJournalInfo>
<CitationSubset>IM</CitationSubset>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">ACE2</Keyword>
<Keyword MajorTopicYN="N">CTD</Keyword>
<Keyword MajorTopicYN="N">SARS-CoV-2</Keyword>
<Keyword MajorTopicYN="N">crystal structure</Keyword>
<Keyword MajorTopicYN="N">immunogenicity</Keyword>
<Keyword MajorTopicYN="N">receptor</Keyword>
<Keyword MajorTopicYN="N">receptor binding domain</Keyword>
</KeywordList>
<CoiStatement>Declaration of Interests The authors declare no competing interests.</CoiStatement>
</MedlineCitation>
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<Day>28</Day>
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<Month>03</Month>
<Day>14</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2020</Year>
<Month>03</Month>
<Day>19</Day>
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<Day>11</Day>
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<affiliations><list><country><li>République populaire de Chine</li>
</country>
<region><li>Anhui</li>
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<tree><country name="République populaire de Chine"><noRegion><name sortKey="Wang, Qihui" sort="Wang, Qihui" uniqKey="Wang Q" first="Qihui" last="Wang">Qihui Wang</name>
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<name sortKey="Hu, Yu" sort="Hu, Yu" uniqKey="Hu Y" first="Yu" last="Hu">Yu Hu</name>
<name sortKey="Lu, Guangwen" sort="Lu, Guangwen" uniqKey="Lu G" first="Guangwen" last="Lu">Guangwen Lu</name>
<name sortKey="Niu, Sheng" sort="Niu, Sheng" uniqKey="Niu S" first="Sheng" last="Niu">Sheng Niu</name>
<name sortKey="Qi, Jianxun" sort="Qi, Jianxun" uniqKey="Qi J" first="Jianxun" last="Qi">Jianxun Qi</name>
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<name sortKey="Song, Chunli" sort="Song, Chunli" uniqKey="Song C" first="Chunli" last="Song">Chunli Song</name>
<name sortKey="Wang, Qisheng" sort="Wang, Qisheng" uniqKey="Wang Q" first="Qisheng" last="Wang">Qisheng Wang</name>
<name sortKey="Wu, Lili" sort="Wu, Lili" uniqKey="Wu L" first="Lili" last="Wu">Lili Wu</name>
<name sortKey="Yan, Jinghua" sort="Yan, Jinghua" uniqKey="Yan J" first="Jinghua" last="Yan">Jinghua Yan</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, Zengyuan" sort="Zhang, Zengyuan" uniqKey="Zhang Z" first="Zengyuan" last="Zhang">Zengyuan Zhang</name>
<name sortKey="Zhou, Huan" sort="Zhou, Huan" uniqKey="Zhou H" first="Huan" last="Zhou">Huan Zhou</name>
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