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-Structure paper
Title | Structural basis of antagonism of human APOBEC3F by HIV-1 Vif. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 26, Issue 12, Page 1176-1183, Year 2019 |
Publish date | Dec 2, 2019 |
Authors | Yingxia Hu / Belete A Desimmie / Henry C Nguyen / Samantha J Ziegler / Tat Cheung Cheng / John Chen / Jia Wang / Hongwei Wang / Kai Zhang / Vinay K Pathak / Yong Xiong / |
PubMed Abstract | HIV-1 virion infectivity factor (Vif) promotes degradation of the antiviral APOBEC3 (A3) proteins through the host ubiquitin-proteasome pathway to enable viral immune evasion. Disrupting Vif-A3 ...HIV-1 virion infectivity factor (Vif) promotes degradation of the antiviral APOBEC3 (A3) proteins through the host ubiquitin-proteasome pathway to enable viral immune evasion. Disrupting Vif-A3 interactions to reinstate the A3-catalyzed suppression of human immunodeficiency virus type 1 (HIV-1) replication is a potential approach for antiviral therapeutics. However, the molecular mechanisms by which Vif recognizes A3 proteins remain elusive. Here we report a cryo-EM structure of the Vif-targeted C-terminal domain of human A3F in complex with HIV-1 Vif and the cellular cofactor core-binding factor beta (CBFβ) at 3.9-Å resolution. The structure shows that Vif and CBFβ form a platform to recruit A3F, revealing a direct A3F-recruiting role of CBFβ beyond Vif stabilization, and captures multiple independent A3F-Vif interfaces. Together with our biochemical and cellular studies, our structural findings establish the molecular determinants that are critical for Vif-mediated neutralization of A3F and provide a comprehensive framework of how HIV-1 Vif hijacks the host protein degradation machinery to counteract viral restriction by A3F. |
External links | Nat Struct Mol Biol / PubMed:31792451 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.9 - 5.0 Å |
Structure data | EMDB-9380, PDB-6nil: EMDB-9381: |
Chemicals | ChemComp-ZN: |
Source |
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Keywords | ANTIVIRAL PROTEIN / Human antiviral restriction factor / HIV viral protein |