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8C0Y

SARS-CoV2 Omicron BA.1 RBD in complex with CAB-A17 antibody

Summary for 8C0Y
Entry DOI10.2210/pdb8c0y/pdb
EMDB information16375
DescriptorSpike protein S2', CAB-A17 antibody (variable) (3 entities in total)
Functional Keywordsantibody, spike, complex, viral protein
Biological sourceSevere acute respiratory syndrome coronavirus 2
More
Total number of polymer chains3
Total formula weight46177.57
Authors
Das, H.,Hallberg, B.M. (deposition date: 2022-12-19, release date: 2024-06-19, Last modification date: 2024-11-13)
Primary citationSheward, D.J.,Pushparaj, P.,Das, H.,Greaney, A.J.,Kim, C.,Kim, S.,Hanke, L.,Hyllner, E.,Dyrdak, R.,Lee, J.,Dopico, X.C.,Dosenovic, P.,Peacock, T.P.,McInerney, G.M.,Albert, J.,Corcoran, M.,Bloom, J.D.,Murrell, B.,Karlsson Hedestam, G.B.,Hallberg, B.M.
Structural basis of broad SARS-CoV-2 cross-neutralization by affinity-matured public antibodies.
Cell Rep Med, 5:101577-101577, 2024
Cited by
PubMed Abstract: Descendants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant now account for almost all SARS-CoV-2 infections. The Omicron variant and its sublineages have spike glycoproteins that are highly diverged from the pandemic founder and first-generation vaccine strain, resulting in significant evasion from monoclonal antibody therapeutics and vaccines. Understanding how commonly elicited antibodies can broaden to cross-neutralize escape variants is crucial. We isolate IGHV3-53, using "public" monoclonal antibodies (mAbs) from an individual 7 months post infection with the ancestral virus and identify antibodies that exhibit potent and broad cross-neutralization, extending to the BA.1, BA.2, and BA.4/BA.5 sublineages of Omicron. Deep mutational scanning reveals these mAbs' high resistance to viral escape. Structural analysis via cryoelectron microscopy of a representative broadly neutralizing antibody, CAB-A17, in complex with the Omicron BA.1 spike highlights the structural underpinnings of this broad neutralization. By reintroducing somatic hypermutations into a germline-reverted CAB-A17, we delineate the role of affinity maturation in the development of cross-neutralization by a public class of antibodies.
PubMed: 38761799
DOI: 10.1016/j.xcrm.2024.101577
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (2.68 Å)
Structure validation

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