8C2R

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

8C2R の概要

• エントリーDOI: 10.2210/pdb8c2r/pdb
• EMDBエントリー: 16375 16397
• 分子名称: Spike glycoprotein, CAB-A17 antibody (LC), CAB-A17 antibody (HC), ... (5 entities in total)
• 機能のキーワード: antibody, spike, complex, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2; 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 477924.61

構造登録者

Das, H.,Hallberg, B.M. (登録日: 2022-12-22, 公開日: 2024-05-22, 最終更新日: 2024-12-04)

主引用文献

Sheward, 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

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

実験手法

ELECTRON MICROSCOPY (2.56 Å)