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TitleStructural insights into RNA bridging between HIV-1 Vif and antiviral factor APOBEC3G.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 4037, Year 2023
Publish dateJul 7, 2023
AuthorsTakahide Kouno / Satoshi Shibata / Megumi Shigematsu / Jaekyung Hyun / Tae Gyun Kim / Hiroshi Matsuo / Matthias Wolf /
PubMed AbstractGreat effort has been devoted to discovering the basis of A3G-Vif interaction, the key event of HIV's counteraction mechanism to evade antiviral innate immune response. Here we show reconstitution of ...Great effort has been devoted to discovering the basis of A3G-Vif interaction, the key event of HIV's counteraction mechanism to evade antiviral innate immune response. Here we show reconstitution of the A3G-Vif complex and subsequent A3G ubiquitination in vitro and report the cryo-EM structure of the A3G-Vif complex at 2.8 Å resolution using solubility-enhanced variants of A3G and Vif. We present an atomic model of the A3G-Vif interface, which assembles via known amino acid determinants. This assembly is not achieved by protein-protein interaction alone, but also involves RNA. The cryo-EM structure and in vitro ubiquitination assays identify an adenine/guanine base preference for the interaction and a unique Vif-ribose contact. This establishes the biological significance of an RNA ligand. Further assessment of interactions between A3G, Vif, and RNA ligands show that the A3G-Vif assembly and subsequent ubiquitination can be controlled by amino acid mutations at the interface or by polynucleotide modification, suggesting that a specific chemical moiety would be a promising pharmacophore to inhibit the A3G-Vif interaction.
External linksNat Commun / PubMed:37419875 / PubMed Central
MethodsEM (single particle)
Resolution2.5 - 4.2 Å
Structure data

34412

8h0i

EMDB-34412, PDB-8h0i:
Cryo-EM structure of APOBEC3G-Vif complex
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-35997: Cryo-EM structure of APOBEC3G-Vif complex
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-35998: Cryo-EM structure of APOBEC3G-Vif complex
Method: EM (single particle) / Resolution: 3.9 Å

35999

8j62

EMDB-35999, PDB-8j62:
Cryo-EM structure of APOBEC3G-Vif complex
Method: EM (single particle) / Resolution: 2.5 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-CL:
Unknown entry / Chloride

Source
  • human immunodeficiency virus 1
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsANTIVIRAL PROTEIN / Human antiviral protein HIV / Human antiviral protein / HIV

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