8szk

From Proteopedia

The cryo-EM structure of PPP2R5A/HIV-1 Vif/CBFb/EloB/EloC complex

PDB ID 8szk

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Structural highlights

8szk is a 5 chain structure with sequence from Homo sapiens and Human immunodeficiency virus type 1 (NEW YORK-5 ISOLATE). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.58Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

2A5A_HUMAN The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment.

Publication Abstract from PubMed

HIV-1 Vif recruits host cullin-RING-E3 ubiquitin ligase and CBFbeta 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-CBFbeta-elongin B-elongin C at 3.58 A 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.

Structural insights into PPP2R5A degradation by HIV-1 Vif.,Hu Y, Delviks-Frankenberry KA, Wu C, Arizaga F, Pathak VK, Xiong Y Nat Struct Mol Biol. 2024 May 24. doi: 10.1038/s41594-024-01314-6. PMID:38789685^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hu Y, Delviks-Frankenberry KA, Wu C, Arizaga F, Pathak VK, Xiong Y. Structural insights into PPP2R5A degradation by HIV-1 Vif. Nat Struct Mol Biol. 2024 May 24. PMID:38789685 doi:10.1038/s41594-024-01314-6