6XCM

Structure of the SARS-CoV-2 spike glycoprotein in complex with the C105 neutralizing antibody Fab fragment (state 1)

Summary for 6XCM

• Entry DOI: 10.2210/pdb6xcm/pdb
• EMDB information: 22127 22128
• Descriptor: Spike glycoprotein, C105 Fab Heavy Chain, C105 Fab Light Chain, ... (8 entities in total)
• Functional Keywords: sars-cov-2, spike glycoprotein, covid-19, monoclonal neutralizing antibody, fabs, nsempem, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 7
• Total formula weight: 527029.15

Authors

Barnes, C.O.,Bjorkman, P.J. (deposition date: 2020-06-08, release date: 2020-07-01, Last modification date: 2024-10-16)

Primary citation

Barnes, C.O.,West Jr., A.P.,Huey-Tubman, K.E.,Hoffmann, M.A.G.,Sharaf, N.G.,Hoffman, P.R.,Koranda, N.,Gristick, H.B.,Gaebler, C.,Muecksch, F.,Lorenzi, J.C.C.,Finkin, S.,Hagglof, T.,Hurley, A.,Millard, K.G.,Weisblum, Y.,Schmidt, F.,Hatziioannou, T.,Bieniasz, P.D.,Caskey, M.,Robbiani, D.F.,Nussenzweig, M.C.,Bjorkman, P.J.
Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies.
Cell, 182:828-, 2020

PubMed Abstract: 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.

PubMed: 32645326
DOI: 10.1016/j.cell.2020.06.025

Experimental method

ELECTRON MICROSCOPY (3.42 Å)