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Publication Abstract from PubMed

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.

Structure of the Vif-binding domain of the antiviral enzyme APOBEC3G.,Kouno T, Luengas EM, Shigematsu M, Shandilya SM, Zhang J, Chen L, Hara M, Schiffer CA, Harris RS, Matsuo H Nat Struct Mol Biol. 2015 May 18. doi: 10.1038/nsmb.3033. PMID:25984970^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.