Abstract：
: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.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Kouno T,Luengas EM,Shigematsu M,Shandilya SM,Zhang J,Chen L,Hara M,Schiffer CA,Harris RS,Matsuo Hdoi
10.1038/nsmb.3033subject
Has Abstractpub_date
2015-06-01 00:00:00pages
485-91issue
6eissn
1545-9993issn
1545-9985pii
nsmb.3033journal_volume
22pub_type
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