EMD-21111

Single-particle
3.0 Å
EMD-21111 Deposition: 12/12/2019
Map released: 05/02/2020
Last modified: 16/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-21111

VRC01 Bound BG505 F14 HIV-1 SOSIP Envelope Trimer Structure

EMD-21111

Single-particle
3.0 Å
EMD-21111 Deposition: 12/12/2019
Map released: 05/02/2020
Last modified: 16/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Human immunodeficiency virus 1, Homo sapiens
Sample: Complex between VRC01 and BG505 F14 HIV-1 SOSIP Env Trimer
Fitted models: 6v8x (Avg. Q-score: 0.401)

Deposition Authors: Henderson R , Acharya P , Bartesaghi A, Zhou Y
Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements.
PUBMED: 31980614
DOI: doi:10.1038/s41467-019-14196-w
ISSN: 2041-1723
Abstract:
The trimeric HIV-1 Envelope protein (Env) mediates viral-host cell fusion via a network of conformational transitions, with allosteric elements in each protomer orchestrating host receptor-induced exposure of the co-receptor binding site and fusion elements. To understand the molecular details of this allostery, here, we introduce Env mutations aimed to prevent CD4-induced rearrangements in the HIV-1 BG505 Env trimer. Binding analysis and single-molecule Förster Resonance Energy Transfer confirm that these mutations prevent CD4-induced transitions of the HIV-1 Env. Structural analysis by single-particle cryo-electron microscopy performed on the BG505 SOSIP mutant Env proteins shows rearrangements in the gp120 topological layer contacts with gp41. Displacement of a conserved tryptophan (W571) from its typical pocket in these Env mutants renders the Env insensitive to CD4 binding. These results reveal the critical function of W571 as a conformational switch in Env allostery and receptor-mediated viral entry and provide insights on Env conformation that are relevant for vaccine design.