Structure of the Vif-binding domain of the antiviral enzyme APOBEC3G
Luengas, Elizabeth M.
Schiffer, Celia A.
Harris, Reuben S.
UMass Chan AffiliationsDepartment of Biochemistry and Molecular Pharmacology
Document TypeJournal Article
DNA Mutational Analysis
Magnetic Resonance Spectroscopy
Protein Interaction Mapping
vif Gene Products, Human Immunodeficiency Virus
Medicinal Chemistry and Pharmaceutics
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AbstractThe 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.
SourceNat 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
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/48905
Related ResourcesLink to Article in PubMed