6UUM

Crystal structure of antibody 438-B11 DSS mutant (Cys98A-Cys100aA)

6UUM の概要

• エントリーDOI: 10.2210/pdb6uum/pdb
• 関連するPDBエントリー: 6UTK
• 分子名称: B11 Fab Light Chain, B11 DSS Fab Heavy Chain, TETRAETHYLENE GLYCOL, ... (7 entities in total)
• 機能のキーワード: v3 glycan supersite, human antibody, immune system, anti-hiv1 neutralizing antibody, viral protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 101775.26

構造登録者

Kumar, S.,Wilson, I.A. (登録日: 2019-10-30, 公開日: 2020-09-23, 最終更新日: 2024-11-20)

主引用文献

Kumar, S.,Ju, B.,Shapero, B.,Lin, X.,Ren, L.,Zhang, L.,Li, D.,Zhou, Z.,Feng, Y.,Sou, C.,Mann, C.J.,Hao, Y.,Sarkar, A.,Hou, J.,Nunnally, C.,Hong, K.,Wang, S.,Ge, X.,Su, B.,Landais, E.,Sok, D.,Zwick, M.B.,He, L.,Zhu, J.,Wilson, I.A.,Shao, Y.
A V H 1-69 antibody lineage from an infected Chinese donor potently neutralizes HIV-1 by targeting the V3 glycan supersite.
Sci Adv, 6:-, 2020

PubMed Abstract: An oligomannose patch around the V3 base of HIV-1 envelope glycoprotein (Env) is recognized by multiple classes of broadly neutralizing antibodies (bNAbs). Here, we investigated the bNAb response to the V3 glycan supersite in an HIV-1-infected Chinese donor by Env-specific single B cell sorting, structural and functional studies, and longitudinal analysis of antibody and virus repertoires. Monoclonal antibodies 438-B11 and 438-D5 were isolated that potently neutralize HIV-1 with moderate breadth, are encoded by the V1-69 germline gene, and have a disulfide-linked long HCDR3 loop. Crystal structures of Env-bound and unbound antibodies revealed heavy chain-mediated recognition of the glycan supersite with a unique angle of approach and a critical role of the intra-HCDR3 disulfide. The mechanism of viral escape was examined via single-genome amplification/sequencing and glycan mutations around the N332 supersite. Our findings further emphasize the V3 glycan supersite as a prominent target for Env-based vaccine design.

PubMed: 32938661
DOI: 10.1126/sciadv.abb1328

実験手法

X-RAY DIFFRACTION (2.1 Å)