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-Structure paper
| タイトル | Structural insights into PPP2R5A degradation by HIV-1 Vif. |
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| ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 31, Issue 10, Page 1492-1501, Year 2024 |
| 掲載日 | 2024年5月24日 |
著者 | Yingxia Hu / Krista A Delviks-Frankenberry / Chunxiang Wu / Fidel Arizaga / Vinay K Pathak / Yong Xiong / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Nat Struct Mol Biol / PubMed:38789685 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 3.58 Å |
| 構造データ | EMDB-40919, PDB-8szk: |
| 由来 |
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キーワード | VIRAL PROTEIN / HIV Vif / Cul5 E3 ligase / PPP2R5A |
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homo sapiens (ヒト)
human immunodeficiency virus type 1 (new york-5 isolate) (ヒト免疫不全ウイルス)
キーワード