8J62

Cryo-EM structure of APOBEC3G-Vif complex

Summary for 8J62

• Entry DOI: 10.2210/pdb8j62/pdb
• EMDB information: 35999
• Descriptor: APOBEC3G, Viral infectivity factor, Core binding factor beta, ... (5 entities in total)
• Functional Keywords: human antiviral protein, hiv, antiviral protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 12
• Total formula weight: 247424.41

Authors

Kouno, T.,Shibata, S.,Hyun, J.,Kim, T.G.,Wolf, M. (deposition date: 2023-04-24, release date: 2023-07-19, Last modification date: 2024-07-03)

Primary citation

Kouno, T.,Shibata, S.,Shigematsu, M.,Hyun, J.,Kim, T.G.,Matsuo, H.,Wolf, M.
Structural insights into RNA bridging between HIV-1 Vif and antiviral factor APOBEC3G.
Nat Commun, 14:4037-4037, 2023

PubMed Abstract: 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.

PubMed: 37419875
DOI: 10.1038/s41467-023-39796-5

Experimental method

ELECTRON MICROSCOPY (2.5 Å)