9O2S

BG505-DS SOSIP in complex with 007 bNAb Fabs - Class 2 (2 Fabs bound)

これはPDB形式変換不可エントリーです。

9O2S の概要

• エントリーDOI: 10.2210/pdb9o2s/pdb
• EMDBエントリー: 70020
• 分子名称: Envelope glycoprotein gp120, Envelope glycoprotein gp41, 007 Fab Heavy Chain, ... (9 entities in total)
• 機能のキーワード: antibody, envelope, sosip, 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: 10
• 化学式量合計: 328465.29

構造登録者

DeLaitsch, A.T.,Bjorkman, P.J. (登録日: 2025-04-04, 公開日: 2025-10-01)

主引用文献

Gieselmann, L.,DeLaitsch, A.T.,Rohde, M.,Radford, C.,Worczinski, J.,Momot, A.,Ahmadov, E.,Burger, J.A.,Havenar-Daughton, C.,Deshpande, S.,Giovannoni, F.,Corti, D.,Kreer, C.,Ercanoglu, M.S.,Schommers, P.,Georgiev, I.S.,West, A.P.,Knufer, J.,Stumpf, R.,Kroidl, A.,Geldmacher, C.,Maganga, L.,William, W.,Ntinginya, N.E.,Hoelscher, M.,Yang, Z.,Wei, Q.,Renfrow, M.,Green, T.J.,Novak, J.,van Gils, M.J.,Gristick, H.B.,Gruell, H.,Bloom, J.D.,Seaman, M.S.,Bjorkman, P.J.,Klein, F.
Identification of a broad and potent V3 glycan site bNAb targeting an N332 gp120 glycan-independent epitope.
Biorxiv, 2025

PubMed Abstract: Broadly neutralizing antibodies (bNAbs) against HIV-1 can suppress viremia and inform vaccine development. Here, we characterized 007, a V3 glycan site bNAb exhibiting high levels of antiviral activity against multiclade pseudovirus panels (GeoMean IC = 0.012 μg/mL, breadth = 69%, 217 virus strains) by targeting a N332 glycan-independent V3 epitope, a site of Env vulnerability to which only weakly neutralizing antibodies had previously been identified. Functional analyses demonstrated distinct binding and neutralization profiles compared to classical V3 glycan site bNAbs. A 007 Fab-Env cryo-EM structure revealed contacts with the V3 GD/NIR motif and interactions with N156 and N301 glycans. In contrast to classical V3 bNAbs, 007 binding to Env does not depend on the N332 glycan, rendering it resistant to common escape mutations. Structures of 007 IgG-Env trimer complexes showed two Env trimers crosslinked by three bivalent IgGs, and bivalent 007 IgG was up to ~300-fold more potent than monovalent 007 IgG heterodimer, suggesting a role for avidity in potent neutralization. Finally, in HIV-1-infected humanized mice, 007 caused transient decline of viremia and overcame classical V3 escape mutations, highlighting 007's potential for HIV-1 prevention, therapy, functional cure, and vaccine design.

PubMed: 40964353
DOI: 10.1101/2025.09.05.674437

実験手法

ELECTRON MICROSCOPY (3.2 Å)