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-Structure paper
Title | Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements. |
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Journal, issue, pages | Nat Commun, Vol. 11, Issue 1, Page 520, Year 2020 |
Publish date | Jan 24, 2020 |
Authors | Rory Henderson / Maolin Lu / Ye Zhou / Zekun Mu / Robert Parks / Qifeng Han / Allen L Hsu / Elizabeth Carter / Scott C Blanchard / R J Edwards / Kevin Wiehe / Kevin O Saunders / Mario J Borgnia / Alberto Bartesaghi / Walther Mothes / Barton F Haynes / Priyamvada Acharya / S Munir Alam / |
PubMed 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 ...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. |
External links | Nat Commun / PubMed:31980614 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.9 - 3.0 Å |
Structure data | EMDB-21111, PDB-6v8x: EMDB-21112, PDB-6v8z: |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / Trimer / Complex / Immunogen / HIV-1 / VIRAL PROTEIN-IMMUNE SYSTEM complex |