4JDT

Crystal structure of chimeric germ-line precursor of NIH45-46 Fab in complex with gp120 of 93TH057 HIV-1

4JDT の概要

• エントリーDOI: 10.2210/pdb4jdt/pdb
• 関連するPDBエントリー: 4JDV
• 分子名称: gp120, Fab heavy chain, Fab light chain, ... (5 entities in total)
• 機能のキーワード: ig fold, anti hiv, antibody, immune system complex, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Human Immunodeficiency Virus 1; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 88708.44

構造登録者

Scharf, L.,Diskin, R.,Bjorkman, P.J. (登録日: 2013-02-25, 公開日: 2013-03-20, 最終更新日: 2024-11-20)

主引用文献

Scharf, L.,West, A.P.,Gao, H.,Lee, T.,Scheid, J.F.,Nussenzweig, M.C.,Bjorkman, P.J.,Diskin, R.
Structural basis for HIV-1 gp120 recognition by a germ-line version of a broadly neutralizing antibody.
Proc.Natl.Acad.Sci.USA, 110:6049-6054, 2013

PubMed Abstract: Efforts to design an effective antibody-based vaccine against HIV-1 would benefit from understanding how germ-line B-cell receptors (BCRs) recognize the HIV-1 gp120/gp41 envelope spike. Potent VRC01-like (PVL) HIV-1 antibodies derived from the VH1-2*02 germ-line allele target the conserved CD4 binding site on gp120. A bottleneck for design of immunogens capable of eliciting PVL antibodies is that VH1-2*02 germ-line BCR interactions with gp120 are uncharacterized. Here, we report the structure of a VH1-2*02 germ-line antibody alone and a germ-line heavy-chain/mature light-chain chimeric antibody complexed with HIV-1 gp120. VH1-2*02 residues make extensive contacts with the gp120 outer domain, including all PVL signature and CD4 mimicry interactions, but not critical CDRH3 contacts with the gp120 inner domain and bridging sheet that are responsible for the improved potency of NIH45-46 over closely related clonal variants, such as VRC01. Our results provide insight into initial recognition of HIV-1 by VH1-2*02 germ-line BCRs and may facilitate the design of immunogens tailored to engage and stimulate broad and potent CD4 binding site antibodies.

PubMed: 23524883
DOI: 10.1073/pnas.1303682110

実験手法

X-RAY DIFFRACTION (3.26 Å)