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-Structure paper
タイトル | Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies. |
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ジャーナル・号・ページ | Cell, Vol. 182, Issue 4, Page 828-842.e16, Year 2020 |
掲載日 | 2020年8月20日 |
著者 | Christopher O Barnes / Anthony P West / Kathryn E Huey-Tubman / Magnus A G Hoffmann / Naima G Sharaf / Pauline R Hoffman / Nicholas Koranda / Harry B Gristick / Christian Gaebler / Frauke Muecksch / Julio C Cetrulo Lorenzi / Shlomo Finkin / Thomas Hägglöf / Arlene Hurley / Katrina G Millard / Yiska Weisblum / Fabian Schmidt / Theodora Hatziioannou / Paul D Bieniasz / Marina Caskey / Davide F Robbiani / Michel C Nussenzweig / Pamela J Bjorkman / |
PubMed 要旨 | Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal immunoglobulin Gs (IgGs) and Fabs from COVID- ...Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal immunoglobulin Gs (IgGs) and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their focus on RBD epitopes, recognition of alpha- and beta-coronaviruses, and contributions of avidity to increased binding/neutralization of IgGs over Fabs. Using electron microscopy, we examined specificities of polyclonal plasma Fabs, revealing recognition of both S1 and RBD epitopes on SARS-CoV-2 spike. Moreover, a 3.4 Å cryo-electron microscopy (cryo-EM) structure of a neutralizing monoclonal Fab-spike complex revealed an epitope that blocks ACE2 receptor binding. Modeling based on these structures suggested different potentials for inter-spike crosslinking by IgGs on viruses, and characterized IgGs would not be affected by identified SARS-CoV-2 spike mutations. Overall, our studies structurally define a recurrent anti-SARS-CoV-2 antibody class derived from VH3-53/VH3-66 and similarity to a SARS-CoV VH3-30 antibody, providing criteria for evaluating vaccine-elicited antibodies. |
リンク | Cell / PubMed:32645326 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 1.8 - 21.0 Å |
構造データ | EMDB-22124: EMDB-22125: EMDB-22126: EMDB-22127, PDB-6xcm: EMDB-22128, PDB-6xcn: PDB-6xca: |
化合物 | ChemComp-SO4: ChemComp-HOH: ChemComp-NAG: |
由来 |
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キーワード | IMMUNE SYSTEM / Antibody / SARS-CoV-2 / SARS2 / Coronavirus / Neutralizing / VIRAL PROTEIN/IMMUNE SYSTEM / Spike glycoprotein / COVID-19 / monoclonal neutralizing antibody / Fabs / nsEMPEM / VIRAL PROTEIN-IMMUNE SYSTEM complex |