9CF5

STRUCTURE OF CD4 MIMETIC CJF-III-288 IN COMPLEX WITH BG505 SOSIP.664 HIV-1ENV TRIMER AND 17B FAB

9CF5 の概要

• エントリーDOI: 10.2210/pdb9cf5/pdb
• EMDBエントリー: 45530
• 分子名称: Envelope glycoprotein gp120, Envelope glycoprotein gp41, 17b Fab light chain, ... (9 entities in total)
• 機能のキーワード: hiv-1, fusion, entry, membrane, viral protein, 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: 12
• 化学式量合計: 371664.97

構造登録者

Niu, L.,Tolbert, W.D.,Pazgier, M. (登録日: 2024-06-27, 公開日: 2025-11-19, 最終更新日: 2025-12-03)

主引用文献

Richard, J.,Grunst, M.W.,Niu, L.,Diaz-Salinas, M.A.,Tolbert, W.D.,Marchitto, L.,Zhou, F.,Bourassa, C.,Yang, D.,Chiu, T.J.,Chen, H.C.,Benlarbi, M.,Gottumukkala, S.,Li, W.,Dionne, K.,Belanger, E.,Chatterjee, D.,Medjahed, H.,Hendrickson, W.A.,Sodroski, J.,Lang, Z.C.,Morton, A.J.,Huang, R.K.,Matthies, D.,Smith 3rd, A.B.,Mothes, W.,Munro, J.B.,Pazgier, M.,Finzi, A.
The asymmetric opening of HIV-1 Env by a potent CD4 mimetic enables anti-coreceptor binding site antibodies to mediate ADCC.
Biorxiv, 2024

PubMed Abstract: HIV-1 envelope glycoproteins (Env) from primary HIV-1 isolates typically adopt a pretriggered "closed" conformation that resists to CD4-induced (CD4i) non-neutralizing antibodies (nnAbs) mediating antibody-dependent cellular cytotoxicity (ADCC). CD4-mimetic compounds (CD4mcs) "open-up" Env allowing binding of CD4i nnAbs, thereby sensitizing HIV-1-infected cells to ADCC. Two families of CD4i nnAbs, the anti-cluster A and anti-coreceptor binding site (CoRBS) Abs, are required to mediate ADCC in combination with the indane CD4mc BNM-III-170. Recently, new indoline CD4mcs with improved potency and breadth have been described. Here, we show that the lead indoline CD4mc, CJF-III-288, sensitizes HIV-1-infected cells to ADCC mediated by anti-CoRBS Abs alone, contributing to improved ADCC activity. Structural and conformational analyses reveal that CJF-III-288, in combination with anti-CoRBS Abs, potently stabilizes an asymmetric "open" State-3 Env conformation, This Env conformation orients the anti-CoRBS Ab to improve ADCC activity and therapeutic potential.

PubMed: 39253431
DOI: 10.1101/2024.08.27.609961

実験手法

ELECTRON MICROSCOPY (3.5 Å)