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TitleStructural basis for HIV-1 antagonism of host APOBEC3G via Cullin E3 ligase.
Journal, issue, pagesSci Adv, Vol. 9, Issue 1, Page eade3168, Year 2023
Publish dateJan 4, 2023
AuthorsFumiaki Ito / Ana L Alvarez-Cabrera / Shiheng Liu / Hanjing Yang / Anna Shiriaeva / Z Hong Zhou / Xiaojiang S Chen /
PubMed AbstractHuman 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.
External linksSci Adv / PubMed:36598981 / PubMed Central
MethodsEM (single particle)
Resolution3.57 - 5.4 Å
Structure data

27875

8e40

EMDB-27875, PDB-8e40:
Full-length APOBEC3G in complex with HIV-1 Vif, CBF-beta, and fork RNA
Method: EM (single particle) / Resolution: 3.57 Å

EMDB-27885: APOBEC3G in complex with HIV-1 Vif/CBF-beta/EloB/EloC/Cul5/Rbx2
Method: EM (single particle) / Resolution: 5.4 Å

EMDB-27887: RNA-mediated APOBEC3G dimer
Method: EM (single particle) / Resolution: 4.5 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • human immunodeficiency virus 1
  • macaca mulatta (Rhesus monkey)
  • homo sapiens (human)
  • escherichia coli (E. coli)
KeywordsVIRAL PROTEIN/RNA / Viral protein - human protein complex / ribonucleoprotein complex / VIRAL PROTEIN-RNA complex

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