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Structure of the Vif-binding domain of the antiviral enzyme APOBEC3G
Schiffer Lab Publications
  • Takahide Kouno, University of Massachusetts Medical School
  • Elizabeth M. Luengas, University of Minnesota, Minneapolis
  • Megumi Shigematsu, University of Minnesota, Minneapolis
  • Shivender Shandilya, University of Massachusetts Medical School
  • JingYing Zhang, University of Minnesota, Minneapolis
  • Luan Chen, University of Minnesota, Minneapolis
  • Mayuko Hara, University of Minnesota, Minneapolis
  • Celia A. Schiffer, University of Massachusetts Medical School
  • Reuben S. Harris, University of Minnesota, Minneapolis
  • Hiroshi Matsuo, University of Minnesota, Minneapolis
UMMS Affiliation
Department of Biochemistry and Molecular Pharmacology
Publication Date
Document Type
Cytidine Deaminase; DNA Mutational Analysis; Humans; Magnetic Resonance Spectroscopy; Models, Molecular; Mutant Proteins; Protein Binding; Protein Conformation; Protein Interaction Mapping; vif Gene Products, Human Immunodeficiency Virus

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 alpha1-beta1, beta2-alpha2 and beta4-alpha4 loops. This structure sheds new light on the Vif-A3G interaction and provides critical information for future drug development.

DOI of Published Version
Nat Struct Mol Biol. 2015 Jun;22(6):485-91. doi: 10.1038/nsmb.3033. Epub 2015 May 18. Link to article on publisher's site
Related Resources
Link to Article in PubMed
PubMed ID
Citation Information
Takahide Kouno, Elizabeth M. Luengas, Megumi Shigematsu, Shivender Shandilya, et al.. "Structure of the Vif-binding domain of the antiviral enzyme APOBEC3G" Vol. 22 Iss. 6 (2015) ISSN: 1545-9985 (Linking)
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