8E40

Full-length APOBEC3G in complex with HIV-1 Vif, CBF-beta, and fork RNA

8E40 の概要

• エントリーDOI: 10.2210/pdb8e40/pdb
• EMDBエントリー: 27875 27885 27887
• 分子名称: DNA dC->dU-editing enzyme APOBEC-3G, Virion infectivity factor, Core-binding factor subunit beta, ... (6 entities in total)
• 機能のキーワード: viral protein - human protein complex, ribonucleoprotein complex, viral protein-rna complex, viral protein/rna
• 由来する生物種: Macaca mulatta (Rhesus monkey); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 99974.35

構造登録者

Ito, F.,Alvarez-Cabrera, A.L.,Liu, S.,Yang, H.,Shiriaeva, A.,Zhou, Z.H.,Chen, X.S. (登録日: 2022-08-17, 公開日: 2023-01-11, 最終更新日: 2025-06-04)

主引用文献

Ito, F.,Alvarez-Cabrera, A.L.,Liu, S.,Yang, H.,Shiriaeva, A.,Zhou, Z.H.,Chen, X.S.
Structural basis for HIV-1 antagonism of host APOBEC3G via Cullin E3 ligase.
Sci Adv, 9:eade3168-eade3168, 2023

PubMed Abstract: 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.

PubMed: 36598981
DOI: 10.1126/sciadv.ade3168

実験手法

ELECTRON MICROSCOPY (3.57 Å)