9BDH

Crystal structure of HIV-1 MPER scaffold in complex with antibody Fab Ab45.1

9BDH の概要

• エントリーDOI: 10.2210/pdb9bdh/pdb
• 分子名称: Fab 45.1 Heavy Chain, Fab 45.1 Light Chain, GT10.2, ... (4 entities in total)
• 機能のキーワード: membrane-proximal external region (mper), hiv-1, germline targeting, b cell, germinal center, viral protein
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 65979.11

構造登録者

Lee, C.C.D.,Wilson, I.A. (登録日: 2024-04-11, 公開日: 2025-02-19)

主引用文献

Ray, R.,Schiffner, T.,Wang, X.,Yan, Y.,Rantalainen, K.,Lee, C.D.,Parikh, S.,Reyes, R.A.,Dale, G.A.,Lin, Y.C.,Pecetta, S.,Giguere, S.,Swanson, O.,Kratochvil, S.,Melzi, E.,Phung, I.,Madungwe, L.,Kalyuzhniy, O.,Warner, J.,Weldon, S.R.,Tingle, R.,Lamperti, E.,Kirsch, K.H.,Phelps, N.,Georgeson, E.,Adachi, Y.,Kubitz, M.,Nair, U.,Crotty, S.,Wilson, I.A.,Schief, W.R.,Batista, F.D.
Affinity gaps among B cells in germinal centers drive the selection of MPER precursors.
Nat.Immunol., 25:1083-1096, 2024

PubMed Abstract: Current prophylactic human immunodeficiency virus 1 (HIV-1) vaccine research aims to elicit broadly neutralizing antibodies (bnAbs). Membrane-proximal external region (MPER)-targeting bnAbs, such as 10E8, provide exceptionally broad neutralization, but some are autoreactive. Here, we generated humanized B cell antigen receptor knock-in mouse models to test whether a series of germline-targeting immunogens could drive MPER-specific precursors toward bnAbs. We found that recruitment of 10E8 precursors to germinal centers (GCs) required a minimum affinity for germline-targeting immunogens, but the GC residency of MPER precursors was brief due to displacement by higher-affinity endogenous B cell competitors. Higher-affinity germline-targeting immunogens extended the GC residency of MPER precursors, but robust long-term GC residency and maturation were only observed for MPER-HuGL18, an MPER precursor clonotype able to close the affinity gap with endogenous B cell competitors in the GC. Thus, germline-targeting immunogens could induce MPER-targeting antibodies, and B cell residency in the GC may be regulated by a precursor-competitor affinity gap.

PubMed: 38816616
DOI: 10.1038/s41590-024-01844-7

実験手法

X-RAY DIFFRACTION (3 Å)