期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 22, 期 6, 页码 485-U79出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.3033
关键词
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资金
- US National Institutes of Health [AI073167, GM091743]
- Toyobo Biotechnology Foundation Fellowship
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 alpha 1-beta 1, beta 2-alpha 2 and beta 4-alpha 4 loops. This structure sheds new light on the Vif-A3G interaction and provides critical information for future drug development.
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