Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
Identifieur interne : 000298 ( Pmc/Checkpoint ); précédent : 000297; suivant : 000299Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
Auteurs : Daniel Wrapp [États-Unis] ; Nianshuang Wang [États-Unis] ; Kizzmekia S. Corbett [États-Unis] ; Jory A. Goldsmith [États-Unis] ; Ching-Lin Hsieh [États-Unis] ; Olubukola Abiona [États-Unis] ; Barney S. Graham [États-Unis] ; Jason S. Mclellan [États-Unis]Source :
- Science (New York, N.y.) [ 0036-8075 ] ; 2020.
Abstract
The World Health Organization has declared the outbreak of a novel coronavirus
(2019-nCoV) to be a public health emergency of international concern. The virus binds to
host cells through its trimeric spike glycoprotein, making this protein a key target for
potential therapies and diagnostics. Wrapp
Url:
DOI: 10.1126/science.abb2507
PubMed: 32075877
PubMed Central: 7164637
Affiliations:
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PMC:7164637Le document en format XML
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conformation</title><author><name sortKey="Wrapp, Daniel" sort="Wrapp, Daniel" uniqKey="Wrapp D" first="Daniel" last="Wrapp">Daniel Wrapp</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712</wicri:regionArea><placeName><region type="state">Texas</region><settlement type="city">Austin (Texas)</settlement></placeName><orgName type="university">Université du Texas à Austin</orgName></affiliation></author><author><name sortKey="Wang, Nianshuang" sort="Wang, Nianshuang" uniqKey="Wang N" first="Nianshuang" last="Wang">Nianshuang Wang</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712</wicri:regionArea><placeName><region type="state">Texas</region><settlement type="city">Austin (Texas)</settlement></placeName><orgName type="university">Université du Texas à Austin</orgName></affiliation></author><author><name sortKey="Corbett, Kizzmekia S" sort="Corbett, Kizzmekia S" uniqKey="Corbett K" first="Kizzmekia S." last="Corbett">Kizzmekia S. 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Graham</name><affiliation wicri:level="2"><nlm:aff id="aff2">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Mclellan, Jason S" sort="Mclellan, Jason S" uniqKey="Mclellan J" first="Jason S." last="Mclellan">Jason S. Mclellan</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712</wicri:regionArea><placeName><region type="state">Texas</region><settlement type="city">Austin (Texas)</settlement></placeName><orgName type="university">Université du Texas à Austin</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32075877</idno><idno type="pmc">7164637</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164637</idno><idno type="RBID">PMC:7164637</idno><idno type="doi">10.1126/science.abb2507</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">001469</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001469</idno><idno type="wicri:Area/Pmc/Curation">001469</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001469</idno><idno type="wicri:Area/Pmc/Checkpoint">000298</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000298</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Cryo-EM structure of the 2019-nCoV spike in the prefusion
conformation</title><author><name sortKey="Wrapp, Daniel" sort="Wrapp, Daniel" uniqKey="Wrapp D" first="Daniel" last="Wrapp">Daniel Wrapp</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712</wicri:regionArea><placeName><region type="state">Texas</region><settlement type="city">Austin (Texas)</settlement></placeName><orgName type="university">Université du Texas à Austin</orgName></affiliation></author><author><name sortKey="Wang, Nianshuang" sort="Wang, Nianshuang" uniqKey="Wang N" first="Nianshuang" last="Wang">Nianshuang Wang</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712</wicri:regionArea><placeName><region type="state">Texas</region><settlement type="city">Austin (Texas)</settlement></placeName><orgName type="university">Université du Texas à Austin</orgName></affiliation></author><author><name sortKey="Corbett, Kizzmekia S" sort="Corbett, Kizzmekia S" uniqKey="Corbett K" first="Kizzmekia S." last="Corbett">Kizzmekia S. Corbett</name><affiliation wicri:level="2"><nlm:aff id="aff2">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Goldsmith, Jory A" sort="Goldsmith, Jory A" uniqKey="Goldsmith J" first="Jory A." last="Goldsmith">Jory A. Goldsmith</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712</wicri:regionArea><placeName><region type="state">Texas</region><settlement type="city">Austin (Texas)</settlement></placeName><orgName type="university">Université du Texas à Austin</orgName></affiliation></author><author><name sortKey="Hsieh, Ching Lin" sort="Hsieh, Ching Lin" uniqKey="Hsieh C" first="Ching-Lin" last="Hsieh">Ching-Lin Hsieh</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712</wicri:regionArea><placeName><region type="state">Texas</region><settlement type="city">Austin (Texas)</settlement></placeName><orgName type="university">Université du Texas à Austin</orgName></affiliation></author><author><name sortKey="Abiona, Olubukola" sort="Abiona, Olubukola" uniqKey="Abiona O" first="Olubukola" last="Abiona">Olubukola Abiona</name><affiliation wicri:level="2"><nlm:aff id="aff2">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Graham, Barney S" sort="Graham, Barney S" uniqKey="Graham B" first="Barney S." last="Graham">Barney S. Graham</name><affiliation wicri:level="2"><nlm:aff id="aff2">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Mclellan, Jason S" sort="Mclellan, Jason S" uniqKey="Mclellan J" first="Jason S." last="Mclellan">Jason S. Mclellan</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712</wicri:regionArea><placeName><region type="state">Texas</region><settlement type="city">Austin (Texas)</settlement></placeName><orgName type="university">Université du Texas à Austin</orgName></affiliation></author></analytic><series><title level="j">Science (New York, N.y.)</title><idno type="ISSN">0036-8075</idno><idno type="eISSN">1095-9203</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Structure of the nCoV trimeric spike</title><p>The World Health Organization has declared the outbreak of a novel coronavirus
(2019-nCoV) to be a public health emergency of international concern. The virus binds to
host cells through its trimeric spike glycoprotein, making this protein a key target for
potential therapies and diagnostics. Wrapp <italic>et al.</italic> determined a
3.5-angstrom-resolution structure of the 2019-nCoV trimeric spike protein by
cryo–electron microscopy. Using biophysical assays, the authors show that this
protein binds at least 10 times more tightly than the corresponding spike protein of
severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor.
They also tested three antibodies known to bind to the SARS-CoV spike protein but did not
detect binding to the 2019-nCoV spike protein. These studies provide valuable information
to guide the development of medical counter-measures for 2019-nCoV.</p><p><italic>Science</italic>, this issue p. <ext-link ext-link-type="doi" xlink:href="10.1126/science.abb2507">1260</ext-link></p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Chan, J F" uniqKey="Chan J">J. F. Chan</name></author><author><name sortKey="Yuan, S" uniqKey="Yuan S">S. Yuan</name></author><author><name sortKey="Kok, K H" uniqKey="Kok K">K.-H. Kok</name></author><author><name sortKey="To, K K W" uniqKey="To K">K. K.-W. To</name></author><author><name sortKey="Chu, H" uniqKey="Chu H">H. Chu</name></author><author><name sortKey="Yang, J" uniqKey="Yang J">J. Yang</name></author><author><name sortKey="Xing, F" uniqKey="Xing F">F. Xing</name></author><author><name sortKey="Liu, J" uniqKey="Liu J">J. Liu</name></author><author><name sortKey="Yip, C C Y" uniqKey="Yip C">C. C.-Y. Yip</name></author><author><name sortKey="Poon, R W S" uniqKey="Poon R">R. W.-S. Poon</name></author><author><name sortKey="Tsoi, H W" uniqKey="Tsoi H">H.-W. Tsoi</name></author><author><name sortKey="Lo, S X0a K F" uniqKey="Lo S">S.
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<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">32075877</article-id><article-id pub-id-type="pmc">7164637</article-id><article-id pub-id-type="publisher-id">abb2507</article-id><article-id pub-id-type="doi">10.1126/science.abb2507</article-id><article-categories><subj-group subj-group-type="article-type"><subject>Report</subject></subj-group><subj-group subj-group-type="heading"><subject>Reports</subject></subj-group><subj-group subj-group-type="legacy-article-type"><subject>Reports</subject></subj-group><subj-group subj-group-type="field"><subject>Biochem</subject><subject>Microbio</subject></subj-group></article-categories><title-group><article-title>Cryo-EM structure of the 2019-nCoV spike in the prefusion
conformation</article-title></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-0538-9647</contrib-id><name><surname>Wrapp</surname><given-names>Daniel</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</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/0000-0002-7569-011X</contrib-id><name><surname>Wang</surname><given-names>Nianshuang</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</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/0000-0002-2641-4688</contrib-id><name><surname>Corbett</surname><given-names>Kizzmekia S.</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Goldsmith</surname><given-names>Jory A.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hsieh</surname><given-names>Ching-Lin</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-2745-1691</contrib-id><name><surname>Abiona</surname><given-names>Olubukola</given-names></name><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/0000-0001-8112-0853</contrib-id><name><surname>Graham</surname><given-names>Barney S.</given-names></name><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/0000-0003-3991-542X</contrib-id><name><surname>McLellan</surname><given-names>Jason S.</given-names></name><xref ref-type="award" rid="award585141"></xref><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1">†</xref></contrib><aff id="aff1"><label>1</label>Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.</aff><aff id="aff2"><label>2</label>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.</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="jmclellan@austin.utexas.edu">jmclellan@austin.utexas.edu</email></corresp></author-notes><pub-date pub-type="ppub"><day>13</day><month>3</month><year>2020</year></pub-date><pub-date pub-type="epub"><day>19</day><month>2</month><year>2020</year></pub-date><volume>367</volume><issue>6483</issue><fpage>1260</fpage><lpage>1263</lpage><history><date date-type="received"><day>10</day><month>2</month><year>2020</year></date><date date-type="accepted"><day>17</day><month>2</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>American Association for the Advancement of Science</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>Structure of the nCoV trimeric spike</title><p>The World Health Organization has declared the outbreak of a novel coronavirus
(2019-nCoV) to be a public health emergency of international concern. The virus binds to
host cells through its trimeric spike glycoprotein, making this protein a key target for
potential therapies and diagnostics. Wrapp <italic>et al.</italic> determined a
3.5-angstrom-resolution structure of the 2019-nCoV trimeric spike protein by
cryo–electron microscopy. Using biophysical assays, the authors show that this
protein binds at least 10 times more tightly than the corresponding spike protein of
severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor.
They also tested three antibodies known to bind to the SARS-CoV spike protein but did not
detect binding to the 2019-nCoV spike protein. These studies provide valuable information
to guide the development of medical counter-measures for 2019-nCoV.</p><p><italic>Science</italic>, this issue p. <ext-link ext-link-type="doi" xlink:href="10.1126/science.abb2507">1260</ext-link></p></abstract><abstract abstract-type="teaser"><p>The overall structure of the 2019-nCoV spike (S) protein resembles that of SARS-CoV S,
but 2019-nCoV S binds more tightly to the host receptor.</p></abstract><abstract><p>The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has
been declared a public health emergency of international concern. The CoV spike (S)
glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To
facilitate medical countermeasure development, we determined a 3.5-angstrom-resolution
cryo–electron microscopy structure of the 2019-nCoV S trimer in the prefusion
conformation. The predominant state of the trimer has one of the three receptor-binding
domains (RBDs) rotated up in a receptor-accessible conformation. We also provide
biophysical and structural evidence that the 2019-nCoV S protein binds
angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute
respiratory syndrome (SARS)-CoV S. Additionally, we tested several published SARS-CoV
RBD-specific monoclonal antibodies and found that they do not have appreciable binding to
2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two
RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of
medical countermeasures to address the ongoing public health crisis.</p></abstract><funding-group><award-group id="award585141"><funding-source><institution-wrap><institution-id institution-id-type="doi">http://dx.doi.org/10.13039/100000060</institution-id><institution>National Institute of Allergy and Infectious Diseases</institution></institution-wrap></funding-source><award-id>R01-AI127521</award-id></award-group></funding-group><custom-meta-group><custom-meta><meta-name>Editor</meta-name><meta-value>Valda Vinson</meta-value></custom-meta><custom-meta><meta-name>Copyeditor</meta-name><meta-value>Suzanne White</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li><li>Texas</li></region><settlement><li>Austin (Texas)</li></settlement><orgName><li>Université du Texas à Austin</li></orgName></list><tree><country name="États-Unis"><region name="Texas"><name sortKey="Wrapp, Daniel" sort="Wrapp, Daniel" uniqKey="Wrapp D" first="Daniel" last="Wrapp">Daniel Wrapp</name></region><name sortKey="Abiona, Olubukola" sort="Abiona, Olubukola" uniqKey="Abiona O" first="Olubukola" last="Abiona">Olubukola Abiona</name><name sortKey="Corbett, Kizzmekia S" sort="Corbett, Kizzmekia S" uniqKey="Corbett K" first="Kizzmekia S." last="Corbett">Kizzmekia S. Corbett</name><name sortKey="Goldsmith, Jory A" sort="Goldsmith, Jory A" uniqKey="Goldsmith J" first="Jory A." last="Goldsmith">Jory A. Goldsmith</name><name sortKey="Graham, Barney S" sort="Graham, Barney S" uniqKey="Graham B" first="Barney S." last="Graham">Barney S. Graham</name><name sortKey="Hsieh, Ching Lin" sort="Hsieh, Ching Lin" uniqKey="Hsieh C" first="Ching-Lin" last="Hsieh">Ching-Lin Hsieh</name><name sortKey="Mclellan, Jason S" sort="Mclellan, Jason S" uniqKey="Mclellan J" first="Jason S." last="Mclellan">Jason S. Mclellan</name><name sortKey="Wang, Nianshuang" sort="Wang, Nianshuang" uniqKey="Wang N" first="Nianshuang" last="Wang">Nianshuang Wang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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