Structure of the Vif-binding domain of the antiviral enzyme APOBEC3G

Takahide Kouno, Elizabeth M. Luengas, Megumi Shigematsu, Shivender M D Shandilya, Jingying Zhang, Luan Chen, Mayuko Hara, Celia A. Schiffer, Reuben S. Harris, Hiroshi Matsuo

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


The human APOBEC3G (A3G) DNA cytosine deaminase restricts and hypermutates DNA-based parasites including HIV-1. The viral infectivity factor (Vif) prevents restriction by triggering A3G degradation. Although the structure of the A3G catalytic domain is known, the structure of the N-terminal Vif-binding domain has proven more elusive. Here, we used evolution- and structure-guided mutagenesis to solubilize the Vif-binding domain of A3G, thus permitting structural determination by NMR spectroscopy. A smaller zinc-coordinating pocket and altered helical packing distinguish the structure from previous catalytic-domain structures and help to explain the reported inactivity of this domain. This soluble A3G N-terminal domain is bound by Vif; this enabled mutagenesis and biochemical experiments, which identified a unique Vif-interacting surface formed by the α1-β1, β2-α2 and β4-α4 loops. This structure sheds new light on the Vif-A3G interaction and provides critical information for future drug development.

Original languageEnglish (US)
Pages (from-to)485-491
Number of pages7
JournalNature Structural and Molecular Biology
Issue number6
StatePublished - Jun 3 2015

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