4RQQ

Crystal structure of human Fab PGDM1400, a broadly reactive and potent HIV-1 neutralizing antibody

4RQQ の概要

• エントリーDOI: 10.2210/pdb4rqq/pdb
• 関連するPDBエントリー: 3U1S
• 分子名称: Human anti-HIV-1 antibody PGDM1400 light chain, Human anti-HIV-1 antibody PGDM1400 heavy chain (2 entities in total)
• 機能のキーワード: igg, anti-hiv-1 antibody, hiv-1 env trimer, 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: 151600.06

構造登録者

Julien, J.-P.,Wilson, I.A. (登録日: 2014-11-04, 公開日: 2014-11-19, 最終更新日: 2024-10-30)

主引用文献

Sok, D.,van Gils, M.J.,Pauthner, M.,Julien, J.P.,Saye-Francisco, K.L.,Hsueh, J.,Briney, B.,Lee, J.H.,Le, K.M.,Lee, P.S.,Hua, Y.,Seaman, M.S.,Moore, J.P.,Ward, A.B.,Wilson, I.A.,Sanders, R.W.,Burton, D.R.
Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex.
Proc.Natl.Acad.Sci.USA, 111:17624-17629, 2014

PubMed Abstract: Broadly neutralizing antibodies (bnAbs) targeting the trimer apex of HIV envelope are favored candidates for vaccine design and immunotherapy because of their great neutralization breadth and potency. However, methods of isolating bnAbs against this site have been limited by the quaternary nature of the epitope region. Here we report the use of a recombinant HIV envelope trimer, BG505 SOSIP.664 gp140, as an affinity reagent to isolate quaternary-dependent bnAbs from the peripheral blood mononuclear cells of a chronically infected donor. The newly isolated bnAbs, named "PGDM1400-1412," show a wide range of neutralization breadth and potency. One of these variants, PGDM1400, is exceptionally broad and potent with cross-clade neutralization coverage of 83% at a median IC50 of 0.003 µg/mL. Overall, our results highlight the utility of BG505 SOSIP.664 gp140 as a tool for the isolation of quaternary-dependent antibodies and reveal a mosaic of antibody responses against the trimer apex within a clonal family.

PubMed: 25422458
DOI: 10.1073/pnas.1415789111

実験手法

X-RAY DIFFRACTION (3.1 Å)