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TitleHIV-1 vif mediates ubiquitination of the proximal protomer in the APOBEC3H dimer to induce degradation.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 5879, Year 2025
Publish dateJul 1, 2025
AuthorsKatarzyna A Skorupka / Kazuhiro Matsuoka / Bakar Hassan / Rodolfo Ghirlando / Vanivilasini Balachandran / Ting-Hua Chen / Kylie J Walters / Celia A Schiffer / Matthias Wolf / Yasumasa Iwatani / Hiroshi Matsuo /
PubMed AbstractThe APOBEC3 family of cytidine deaminases restricts retroviruses like HIV-1 by mutating viral DNA. HIV-1 evades this restriction by producing Vif, which recruits the Cullin-5 (CUL5) E3 ubiquitin ...The APOBEC3 family of cytidine deaminases restricts retroviruses like HIV-1 by mutating viral DNA. HIV-1 evades this restriction by producing Vif, which recruits the Cullin-5 (CUL5) E3 ubiquitin ligase complex to promote APOBEC3 degradation. Here we resolve key aspects of this counter-defense mechanism by determining a 3.6 Å cryo-EM structure of chimpanzee APOBEC3H (cpzA3H) in complex with HIV-1 Vif and three components of the CUL5 E3 ligase-CBFβ, EloB, and EloC (VCBC). The structure captures cpzA3H as an RNA-mediated dimer within the cpzA3H-VCBC complex, allowing us to examine the role of dimerization. We find that ubiquitination occurs specifically at two lysine residues on the Vif-proximal protomer, while the distal protomer remains unmodified. The structural model of the active cpzA3H-Vif-CUL5 E3 ligase holoenzyme reveals spatial preferences for ubiquitin transfer to the targeted lysine residues. These findings enhance our understanding of A3H degradation and suggest new antiviral strategies targeting this host-virus interface.
External linksNat Commun / PubMed:40593686 / PubMed Central
MethodsEM (single particle)
Resolution3.58 - 4.0 Å
Structure data

47752

9e93

EMDB-47752, PDB-9e93:
Structural Insights into HIV-1 Vif-Mediated Ubiquitination and Degradation of APOBEC3H
Method: EM (single particle) / Resolution: 3.58 Å

47805

9e9v

EMDB-47805, PDB-9e9v:
Structural Insights into HIV-1 Vif-Mediated Ubiquitination and Degradation of APOBEC3H
Method: EM (single particle) / Resolution: 4.0 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • pan troglodytes (chimpanzee)
  • escherichia coli bl21(de3) (bacteria)
  • homo sapiens (human)
  • human immunodeficiency virus 1
KeywordsVIRAL PROTEIN/RNA / APOBEC3H HIV-1 Vif / VIRAL PROTEIN / VIRAL PROTEIN-RNA complex

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