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TitleStructural basis of antagonism of human APOBEC3F by HIV-1 Vif.
Journal, issue, pagesNat Struct Mol Biol, Vol. 26, Issue 12, Page 1176-1183, Year 2019
Publish dateDec 2, 2019
AuthorsYingxia 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 AbstractHIV-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 linksNat Struct Mol Biol / PubMed:31792451 / PubMed Central
MethodsEM (single particle)
Resolution3.9 - 5.0 Å
Structure data

9380

6nil

EMDB-9380, PDB-6nil:
cryoEM structure of the truncated HIV-1 Vif/CBFbeta/A3F complex
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-9381:
CryoEM reconstruction of the full HIV-1 Vif/CBFbeta/A3F complex
Method: EM (single particle) / Resolution: 5.0 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • human immunodeficiency virus 1
  • homo sapiens (human)
KeywordsANTIVIRAL PROTEIN / Human antiviral restriction factor / HIV viral protein

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