6XCA

Crystal structure of an anti-SARS-CoV-2 human neutralizing antibody Fab fragment, C105

Summary for 6XCA

• Entry DOI: 10.2210/pdb6xca/pdb
• Descriptor: C105 Heavy Chain, C105 Light Chain, SULFATE ION, ... (4 entities in total)
• Functional Keywords: antibody, sars-cov-2, sars2, coronavirus, neutralizing, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 47705.78

Authors

Sharaf, N.G.,Barnes, C.O.,Bjorkman, P.J. (deposition date: 2020-06-08, release date: 2020-07-01, Last modification date: 2024-10-23)

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

X-RAY DIFFRACTION (1.8 Å)