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Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2

Identifieur interne : 000063 ( Pmc/Checkpoint ); précédent : 000062; suivant : 000064

Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2

Auteurs : Renhong Yan [République populaire de Chine] ; Yuanyuan Zhang [République populaire de Chine] ; Yaning Li [République populaire de Chine] ; Lu Xia [République populaire de Chine] ; Yingying Guo [République populaire de Chine] ; Qiang Zhou [République populaire de Chine]

Source :

RBID : PMC:7164635

Abstract

How SARS-CoV-2 binds to human cells

Scientists are racing to learn the secrets of severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), which is the cause of the pandemic disease COVID-19. The first step in viral entry is the binding of the viral trimeric spike protein to the human receptor angiotensin-converting enzyme 2 (ACE2). Yan et al.present the structure of human ACE2 in complex with a membrane protein that it chaperones, B0AT1. In the context of this complex, ACE2 is a dimer. A further structure shows how the receptor binding domain of SARS-CoV-2 interacts with ACE2 and suggests that it is possible that two trimeric spike proteins bind to an ACE2 dimer. The structures provide a basis for the development of therapeutics targeting this crucial interaction.

Science, this issue p. 1444


Url:
DOI: 10.1126/science.abb2762
PubMed: 32132184
PubMed Central: 7164635


Affiliations:


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PMC:7164635

Le document en format XML

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<p>Scientists are racing to learn the secrets of severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), which is the cause of the pandemic disease COVID-19. The first step in viral entry is the binding of the viral trimeric spike protein to the human receptor angiotensin-converting enzyme 2 (ACE2). Yan
<italic>et al.</italic>
present the structure of human ACE2 in complex with a membrane protein that it chaperones, B
<sup>0</sup>
AT1. In the context of this complex, ACE2 is a dimer. A further structure shows how the receptor binding domain of SARS-CoV-2 interacts with ACE2 and suggests that it is possible that two trimeric spike proteins bind to an ACE2 dimer. The structures provide a basis for the development of therapeutics targeting this crucial interaction.</p>
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<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Science</journal-id>
<journal-id journal-id-type="iso-abbrev">Science</journal-id>
<journal-id journal-id-type="publisher-id">SCIENCE</journal-id>
<journal-id journal-id-type="hwp">science</journal-id>
<journal-title-group>
<journal-title>Science (New York, N.y.)</journal-title>
</journal-title-group>
<issn pub-type="ppub">0036-8075</issn>
<issn pub-type="epub">1095-9203</issn>
<publisher>
<publisher-name>American Association for the Advancement of Science</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">32132184</article-id>
<article-id pub-id-type="pmc">7164635</article-id>
<article-id pub-id-type="publisher-id">abb2762</article-id>
<article-id pub-id-type="doi">10.1126/science.abb2762</article-id>
<article-categories>
<subj-group subj-group-type="article-type">
<subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="heading">
<subject>Research Articles</subject>
</subj-group>
<subj-group subj-group-type="legacy-article-type">
<subject>R-Articles</subject>
</subj-group>
<subj-group subj-group-type="field">
<subject>Biochem</subject>
<subject>Cell Biol</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-7122-6547</contrib-id>
<name>
<surname>Yan</surname>
<given-names>Renhong</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-2500-0010</contrib-id>
<name>
<surname>Zhang</surname>
<given-names>Yuanyuan</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="author-notes" rid="afn1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Li</surname>
<given-names>Yaning</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
<xref ref-type="author-notes" rid="afn1">*</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0003-3007-3086</contrib-id>
<name>
<surname>Xia</surname>
<given-names>Lu</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Guo</surname>
<given-names>Yingying</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-6237-8813</contrib-id>
<name>
<surname>Zhou</surname>
<given-names>Qiang</given-names>
</name>
<xref ref-type="award" rid="award586138"></xref>
<xref ref-type="award" rid="award594232"></xref>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="corresp" rid="cor1"></xref>
</contrib>
<aff id="aff1">
<label>1</label>
Key Laboratory of Structural Biology of Zhejiang Province, Institute of Biology, Westlake Institute for Advanced Study, 18 Shilongshan Road, Hangzhou 310024, Zhejiang Province, China.</aff>
<aff id="aff2">
<label>2</label>
School of Life Sciences, Westlake University, 18 Shilongshan Road, Hangzhou 310024, Zhejiang Province, China.</aff>
<aff id="aff3">
<label>3</label>
Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.</aff>
</contrib-group>
<author-notes>
<fn id="afn1" fn-type="equal">
<label>*</label>
<p>These authors contributed equally to this work.</p>
</fn>
<corresp id="cor1">
<label></label>
Corresponding author. Email:
<email xlink:href="zhouqiang@westlake.edu.cn">zhouqiang@westlake.edu.cn</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub">
<day>27</day>
<month>3</month>
<year>2020</year>
</pub-date>
<pub-date pub-type="epub">
<day>04</day>
<month>3</month>
<year>2020</year>
</pub-date>
<volume>367</volume>
<issue>6485</issue>
<fpage>1444</fpage>
<lpage>1448</lpage>
<history>
<date date-type="received">
<day>12</day>
<month>2</month>
<year>2020</year>
</date>
<date date-type="accepted">
<day>03</day>
<month>3</month>
<year>2020</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works</copyright-statement>
<copyright-year>2020</copyright-year>
<copyright-holder>AAAS</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/">
<ali:license_ref specific-use="vor" start_date="2020-03-04">https://creativecommons.org/licenses/by/4.0/</ali:license_ref>
<license-p>This open access article is distributed under
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License 4.0 (CC BY)</ext-link>
.</license-p>
</license>
</permissions>
<abstract abstract-type="editor">
<title>How SARS-CoV-2 binds to human cells</title>
<p>Scientists are racing to learn the secrets of severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), which is the cause of the pandemic disease COVID-19. The first step in viral entry is the binding of the viral trimeric spike protein to the human receptor angiotensin-converting enzyme 2 (ACE2). Yan
<italic>et al.</italic>
present the structure of human ACE2 in complex with a membrane protein that it chaperones, B
<sup>0</sup>
AT1. In the context of this complex, ACE2 is a dimer. A further structure shows how the receptor binding domain of SARS-CoV-2 interacts with ACE2 and suggests that it is possible that two trimeric spike proteins bind to an ACE2 dimer. The structures provide a basis for the development of therapeutics targeting this crucial interaction.</p>
<p>
<italic>Science</italic>
, this issue p.
<ext-link ext-link-type="doi" xlink:href="10.1126/science.abb2762">1444</ext-link>
</p>
</abstract>
<abstract abstract-type="teaser">
<p>Insight into how SARS-CoV-2 binds its human receptor could provide a basis for the development of therapeutics.</p>
</abstract>
<abstract>
<p>Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for severe acute respiratory syndrome–coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious coronavirus disease 2019 (COVID-19) epidemic. Here, we present cryo–electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B
<sup>0</sup>
AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resolution of 2.9 angstroms, with a local resolution of 3.5 angstroms at the ACE2-RBD interface. The ACE2-B
<sup>0</sup>
AT1 complex is assembled as a dimer of heterodimers, with the collectrin-like domain of ACE2 mediating homodimerization. The RBD is recognized by the extracellular peptidase domain of ACE2 mainly through polar residues. These findings provide important insights into the molecular basis for coronavirus recognition and infection.</p>
</abstract>
<funding-group>
<award-group id="award586138">
<funding-source>
<institution-wrap>
<institution-id institution-id-type="doi">http://dx.doi.org/10.13039/501100001809</institution-id>
<institution>National Natural Science Foundation of China</institution>
</institution-wrap>
</funding-source>
<award-id>31971123</award-id>
</award-group>
<award-group id="award586141">
<funding-source>
<institution-wrap>
<institution-id institution-id-type="doi">http://dx.doi.org/10.13039/501100001809</institution-id>
<institution>National Natural Science Foundation of China</institution>
</institution-wrap>
</funding-source>
<award-id>81920108015</award-id>
</award-group>
<award-group id="award586171">
<funding-source>
<institution-wrap>
<institution-id institution-id-type="doi">http://dx.doi.org/10.13039/501100001809</institution-id>
<institution>National Natural Science Foundation of China</institution>
</institution-wrap>
</funding-source>
<award-id>31930059</award-id>
</award-group>
<award-group id="award586172">
<funding-source>
<institution-wrap>
<institution>Key R&D Program of Zhejiang Province</institution>
</institution-wrap>
</funding-source>
<award-id>2020C04001</award-id>
</award-group>
<award-group id="award594232">
<funding-source>
<institution-wrap>
<institution>the SARS-CoV-2 emergency project of the Science and Technology Department of Zhejiang Province</institution>
</institution-wrap>
</funding-source>
<award-id>2020C03129</award-id>
</award-group>
</funding-group>
<custom-meta-group>
<custom-meta>
<meta-name>Number-color-figs</meta-name>
<meta-value>5</meta-value>
</custom-meta>
<custom-meta>
<meta-name>Number-figs</meta-name>
<meta-value>5</meta-value>
</custom-meta>
<custom-meta>
<meta-name>Editor</meta-name>
<meta-value>Valda Vinson</meta-value>
</custom-meta>
<custom-meta>
<meta-name>Copyeditor</meta-name>
<meta-value>Amelia Beyna</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
<affiliations>
<list>
<country>
<li>République populaire de Chine</li>
</country>
<settlement>
<li>Pékin</li>
</settlement>
</list>
<tree>
<country name="République populaire de Chine">
<noRegion>
<name sortKey="Yan, Renhong" sort="Yan, Renhong" uniqKey="Yan R" first="Renhong" last="Yan">Renhong Yan</name>
</noRegion>
<name sortKey="Guo, Yingying" sort="Guo, Yingying" uniqKey="Guo Y" first="Yingying" last="Guo">Yingying Guo</name>
<name sortKey="Guo, Yingying" sort="Guo, Yingying" uniqKey="Guo Y" first="Yingying" last="Guo">Yingying Guo</name>
<name sortKey="Li, Yaning" sort="Li, Yaning" uniqKey="Li Y" first="Yaning" last="Li">Yaning Li</name>
<name sortKey="Xia, Lu" sort="Xia, Lu" uniqKey="Xia L" first="Lu" last="Xia">Lu Xia</name>
<name sortKey="Xia, Lu" sort="Xia, Lu" uniqKey="Xia L" first="Lu" last="Xia">Lu Xia</name>
<name sortKey="Yan, Renhong" sort="Yan, Renhong" uniqKey="Yan R" first="Renhong" last="Yan">Renhong Yan</name>
<name sortKey="Zhang, Yuanyuan" sort="Zhang, Yuanyuan" uniqKey="Zhang Y" first="Yuanyuan" last="Zhang">Yuanyuan Zhang</name>
<name sortKey="Zhang, Yuanyuan" sort="Zhang, Yuanyuan" uniqKey="Zhang Y" first="Yuanyuan" last="Zhang">Yuanyuan Zhang</name>
<name sortKey="Zhou, Qiang" sort="Zhou, Qiang" uniqKey="Zhou Q" first="Qiang" last="Zhou">Qiang Zhou</name>
<name sortKey="Zhou, Qiang" sort="Zhou, Qiang" uniqKey="Zhou Q" first="Qiang" last="Zhou">Qiang Zhou</name>
</country>
</tree>
</affiliations>
</record>

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