EMD-21111
VRC01 Bound BG505 F14 HIV-1 SOSIP Envelope Trimer Structure
EMD-21111
Single-particle3.0 Å
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Map released: 05/02/2020
Last modified: 16/10/2024
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
Sample: Complex between VRC01 and BG505 F14 HIV-1 SOSIP Env Trimer
Fitted models: 6v8x (Avg. Q-score: 0.401)
Deposition Authors: Henderson R
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Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements.
Henderson R
,
Lu M
,
Zhou Y
,
Mu Z
,
Parks R,
Han Q
,
Hsu AL
,
Carter E,
Blanchard SC
,
Edwards RJ
,
Wiehe K,
Saunders KO
,
Borgnia MJ
,
Bartesaghi A,
Mothes W,
Haynes BF,
Acharya P
,
Munir Alam S
(2020) Nat Commun , 11 , 520 - 520
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(2020) Nat Commun , 11 , 520 - 520
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.
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.