EMD-44484

Single-particle
3.3 Å
EMD-44484 Deposition: 16/04/2024
Map released: 31/07/2024
Last modified: 23/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-44484

Cryo-EM structure of the HIV-1 BG505 IDL Env trimer in complex with 3BNC117 and 10-1074 Fabs

EMD-44484

Single-particle
3.3 Å
EMD-44484 Deposition: 16/04/2024
Map released: 31/07/2024
Last modified: 23/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Human immunodeficiency virus 1
Sample: Cryo-EM Structure of the HIV-1 BG505 IDL Env trimer in complex with 3BNC117 and 10-1074 Fabs
Fitted models: 9bew (Avg. Q-score: 0.488)

Deposition Authors: Gorman J , Kwong PD
Design of soluble HIV-1 envelope trimers free of covalent gp120-gp41 bonds with prevalent native-like conformation.
PUBMED: 39028623
DOI: doi:10.1016/j.celrep.2024.114518
ISSN: 2211-1247
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.