9BF6

Cryo-EM structure of the HIV-1 WITO IDL Env trimer in complex with PGT122 Fab

Summary for 9BF6

• Entry DOI: 10.2210/pdb9bf6/pdb
• EMDB information: 44482 44484 44491
• Descriptor: Envelope glycoprotein gp41, Envelope glycoprotein gp120, PGT122 heavy chain, ... (9 entities in total)
• Functional Keywords: cd4, hiv-1, sosip, vaccine, gp120, gp41, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1 (HIV-1); More
• Total number of polymer chains: 12
• Total formula weight: 318185.17

Authors

Gorman, J.,Kwong, P.D. (deposition date: 2024-04-16, release date: 2024-07-31, Last modification date: 2024-10-23)

Primary citation

Zhang, P.,Gorman, J.,Tsybovsky, Y.,Lu, M.,Liu, Q.,Gopan, V.,Singh, M.,Lin, Y.,Miao, H.,Seo, Y.,Kwon, A.,Olia, A.S.,Chuang, G.Y.,Geng, H.,Lai, Y.T.,Zhou, T.,Mascola, J.R.,Mothes, W.,Kwong, P.D.,Lusso, P.
Design of soluble HIV-1 envelope trimers free of covalent gp120-gp41 bonds with prevalent native-like conformation.
Cell Rep, 43:114518-114518, 2024

PubMed Abstract: Soluble HIV-1 envelope (Env) trimers may serve as effective vaccine immunogens. The widely utilized SOSIP trimers have been paramount for structural studies, but the disulfide bond they feature between gp120 and gp41 constrains intersubunit mobility and may alter antigenicity. Here, we report an alternative strategy to generate stabilized soluble Env trimers free of covalent gp120-gp41 bonds. Stabilization was achieved by introducing an intrasubunit disulfide bond between the inner and outer domains of gp120, defined as interdomain lock (IDL). Correctly folded IDL trimers displaying a native-like antigenic profile were produced for HIV-1 Envs of different clades. Importantly, the IDL design abrogated CD4 binding while not affecting recognition by potent neutralizing antibodies to the CD4-binding site. By cryoelectron microscopy, IDL trimers were shown to adopt a closed prefusion configuration, while single-molecule fluorescence resonance energy transfer documented a high prevalence of native-like conformation. Thus, IDL trimers may be promising candidates as vaccine immunogens.

PubMed: 39028623
DOI: 10.1016/j.celrep.2024.114518

Experimental method

ELECTRON MICROSCOPY (4.5 Å)