Summary information and primary citation
- PDB-id
- 8e40; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- viral protein-RNA
- Method
- cryo-EM (3.57 Å)
- Summary
- Full-length apobec3g in complex with hiv-1 vif, cbf-beta, and fork RNA
- Reference
- Ito F, Alvarez-Cabrera AL, Liu S, Yang H, Shiriaeva A, Zhou ZH, Chen XS (2023): "Structural basis for HIV-1 antagonism of host APOBEC3G via Cullin E3 ligase." Sci Adv, 9, eade3168. doi: 10.1126/sciadv.ade3168.
- 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.
