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-Structure paper
タイトル | Structural basis for HIV-1 antagonism of host APOBEC3G via Cullin E3 ligase. |
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ジャーナル・号・ページ | Sci Adv, Vol. 9, Issue 1, Page eade3168, Year 2023 |
掲載日 | 2023年1月4日 |
著者 | Fumiaki Ito / Ana L Alvarez-Cabrera / Shiheng Liu / Hanjing Yang / Anna Shiriaeva / Z Hong Zhou / Xiaojiang S Chen / |
PubMed 要旨 | Human APOBEC3G (A3G) is a virus restriction factor that inhibits HIV-1 replication and triggers lethal hypermutation on viral reverse transcripts. HIV-1 viral infectivity factor (Vif) breaches this ...Human APOBEC3G (A3G) is a virus restriction factor that inhibits HIV-1 replication and triggers lethal hypermutation on viral reverse transcripts. HIV-1 viral infectivity factor (Vif) breaches this host A3G immunity by hijacking a cellular E3 ubiquitin ligase complex to target A3G for ubiquitination and degradation. The molecular mechanism of A3G targeting by Vif-E3 ligase is unknown, limiting the antiviral efforts targeting this host-pathogen interaction crucial for HIV-1 infection. Here, we report the cryo-electron microscopy structures of A3G bound to HIV-1 Vif in complex with T cell transcription cofactor CBF-β and multiple components of the Cullin-5 RING E3 ubiquitin ligase. The structures reveal unexpected RNA-mediated interactions of Vif with A3G primarily through A3G's noncatalytic domain, while A3G's catalytic domain is poised for ubiquitin transfer. These structures elucidate the molecular mechanism by which HIV-1 Vif hijacks the host ubiquitin ligase to specifically target A3G to establish infection and offer structural information for the rational development of antiretroviral therapeutics. |
リンク | Sci Adv / PubMed:36598981 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.57 - 5.4 Å |
構造データ | EMDB-27875, PDB-8e40: EMDB-27885: APOBEC3G in complex with HIV-1 Vif/CBF-beta/EloB/EloC/Cul5/Rbx2 EMDB-27887: RNA-mediated APOBEC3G dimer |
化合物 | ChemComp-ZN: |
由来 |
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キーワード | VIRAL PROTEIN/RNA / Viral protein - human protein complex / ribonucleoprotein complex / VIRAL PROTEIN-RNA complex |