8Q5Y

cryoEM structure of SARS-CoV2 Spike trimer in complex with Fab23

8Q5Y の概要

• エントリーDOI: 10.2210/pdb8q5y/pdb
• EMDBエントリー: 18180
• 分子名称: Monoclonal antibody Mab 23 (Light chain), Monoclonal antibody Mab 23 (Heavy Chain), Spike glycoprotein (3 entities in total)
• 機能のキーワード: antibody, spike., viral protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 643764.62

構造登録者

Hallberg, M.,Das, H. (登録日: 2023-08-10, 公開日: 2024-07-17, 最終更新日: 2024-11-20)

主引用文献

Mandolesi, M.,Das, H.,de Vries, L.,Yang, Y.,Kim, C.,Dhinakaran, M.,Castro Dopico, X.,Fischbach, J.,Kim, S.,Guryleva, M.V.,Adori, M.,Chernyshev, M.,Stalmarck, A.,Hanke, L.,McInerney, G.M.,Sheward, D.J.,Corcoran, M.,Hallberg, B.M.,Murrell, B.,Karlsson Hedestam, G.B.
Multi-compartmental diversification of neutralizing antibody lineages dissected in SARS-CoV-2 spike-immunized macaques.
Nat Commun, 15:6338-6338, 2024

PubMed Abstract: The continued evolution of SARS-CoV-2 underscores the need to understand qualitative aspects of the humoral immune response elicited by spike immunization. Here, we combine monoclonal antibody (mAb) isolation with deep B cell receptor (BCR) repertoire sequencing of rhesus macaques immunized with prefusion-stabilized spike glycoprotein. Longitudinal tracing of spike-sorted B cell lineages in multiple immune compartments demonstrates increasing somatic hypermutation and broad dissemination of vaccine-elicited B cells in draining and non-draining lymphoid compartments, including the bone marrow, spleen and, most notably, periaortic lymph nodes. Phylogenetic analysis of spike-specific monoclonal antibody lineages identified through deep repertoire sequencing delineates extensive intra-clonal diversification that shaped neutralizing activity. Structural analysis of the spike in complex with a broadly neutralizing mAb provides a molecular basis for the observed differences in neutralization breadth between clonally related antibodies. Our findings highlight that immunization leads to extensive intra-clonal B cell evolution where members of the same lineage can both retain the original epitope specificity and evolve to recognize additional spike variants not previously encountered.

PubMed: 39068149
DOI: 10.1038/s41467-024-50286-0

実験手法

ELECTRON MICROSCOPY (2.6 Å)