6O42

Crystal structure of the germline PGZL1 (PGZL1_gVmDmJ) Fab in complex with MPER peptide epitope.

6O42 の概要

• エントリーDOI: 10.2210/pdb6o42/pdb
• 関連するPDBエントリー: 6O3D 6O3G 6O3J 6O3K 6O3L 6O3U 6O41
• 分子名称: PGZL1_gVmDmJ light chain, PGZL1_gVmDmJ heavy chain, MPER peptide, region 671-683 of HIV-1 gp41, ... (6 entities in total)
• 機能のキーワード: germline pgzl1 anti hiv-1, gp41 mper, membrane lipids, broadly neutralising hiv-1 antibody, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 99589.31

構造登録者

Irimia, A.,Wilson, I.A. (登録日: 2019-02-27, 公開日: 2019-12-04, 最終更新日: 2024-10-23)

主引用文献

Zhang, L.,Irimia, A.,He, L.,Landais, E.,Rantalainen, K.,Leaman, D.P.,Vollbrecht, T.,Stano, A.,Sands, D.I.,Kim, A.S.,Poignard, P.,Burton, D.R.,Murrell, B.,Ward, A.B.,Zhu, J.,Wilson, I.A.,Zwick, M.B.
An MPER antibody neutralizes HIV-1 using germline features shared among donors.
Nat Commun, 10:5389-5389, 2019

PubMed Abstract: The membrane-proximal external region (MPER) of HIV-1 envelope glycoprotein (Env) can be targeted by neutralizing antibodies of exceptional breadth. MPER antibodies usually have long, hydrophobic CDRH3s, lack activity as inferred germline precursors, are often from the minor IgG3 subclass, and some are polyreactive, such as 4E10. Here we describe an MPER broadly neutralizing antibody from the major IgG1 subclass, PGZL1, which shares germline V/D-region genes with 4E10, has a shorter CDRH3, and is less polyreactive. A recombinant sublineage variant pan-neutralizes a 130-isolate panel at 1.4 μg/ml (IC). Notably, a germline revertant with mature CDR3s neutralizes 12% of viruses and still binds MPER after DJ reversion. Crystal structures of lipid-bound PGZL1 variants and cryo-EM reconstruction of an Env-PGZL1 complex reveal how these antibodies recognize MPER and viral membrane. Discovery of common genetic and structural elements among MPER antibodies from different patients suggests that such antibodies could be elicited using carefully designed immunogens.

PubMed: 31772165
DOI: 10.1038/s41467-019-12973-1

実験手法

X-RAY DIFFRACTION (2.6 Å)