8H0I

Cryo-EM structure of APOBEC3G-Vif complex

8H0I の概要

• エントリーDOI: 10.2210/pdb8h0i/pdb
• EMDBエントリー: 34412
• 分子名称: APOBEC3G, Viral infectivity factor, Core binding factor beta, ... (6 entities in total)
• 機能のキーワード: human antiviral protein hiv, antiviral protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 248320.80

構造登録者

Kouno, T.,Shibata, S.,Hyun, J.,Kim, T.G.,Wolf, M. (登録日: 2022-09-29, 公開日: 2023-07-19, 最終更新日: 2024-07-03)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (2.8 Å)