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TitleStructural insights into PPP2R5A degradation by HIV-1 Vif.
Journal, issue, pagesNat Struct Mol Biol, Vol. 31, Issue 10, Page 1492-1501, Year 2024
Publish dateMay 24, 2024
AuthorsYingxia Hu / Krista A Delviks-Frankenberry / Chunxiang Wu / Fidel Arizaga / Vinay K Pathak / Yong Xiong /
PubMed AbstractHIV-1 Vif recruits host cullin-RING-E3 ubiquitin ligase and CBFβ to degrade the cellular APOBEC3 antiviral proteins through diverse interactions. Recent evidence has shown that Vif also degrades the ...HIV-1 Vif recruits host cullin-RING-E3 ubiquitin ligase and CBFβ to degrade the cellular APOBEC3 antiviral proteins through diverse interactions. Recent evidence has shown that Vif also degrades the regulatory subunits PPP2R5(A-E) of cellular protein phosphatase 2A to induce G2/M cell cycle arrest. As PPP2R5 proteins bear no functional or structural resemblance to A3s, it is unclear how Vif can recognize different sets of proteins. Here we report the cryogenic-electron microscopy structure of PPP2R5A in complex with HIV-1 Vif-CBFβ-elongin B-elongin C at 3.58 Å resolution. The structure shows PPP2R5A binds across the Vif molecule, with biochemical and cellular studies confirming a distinct Vif-PPP2R5A interface that partially overlaps with those for A3s. Vif also blocks a canonical PPP2R5A substrate-binding site, indicating that it suppresses the phosphatase activities through both degradation-dependent and degradation-independent mechanisms. Our work identifies critical Vif motifs regulating the recognition of diverse A3 and PPP2R5A substrates, whereby disruption of these host-virus protein interactions could serve as potential targets for HIV-1 therapeutics.
External linksNat Struct Mol Biol / PubMed:38789685 / PubMed Central
MethodsEM (single particle)
Resolution3.58 Å
Structure data

40919

8szk

EMDB-40919, PDB-8szk:
The cryo-EM structure of PPP2R5A/HIV-1 Vif/CBFb/EloB/EloC complex
Method: EM (single particle) / Resolution: 3.58 Å

Source
  • homo sapiens (human)
  • human immunodeficiency virus type 1 (new york-5 isolate)
KeywordsVIRAL PROTEIN / HIV Vif / Cul5 E3 ligase / PPP2R5A

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