Structure of the Vif-binding domain of the antiviral enzyme APOBEC3G
Authors
Kouno, TakahideLuengas, Elizabeth M.
Shigematsu, Megumi
Shandilya, Shivender
Zhang, JingYing
Chen, Luan
Hara, Mayuko
Schiffer, Celia A.
Harris, Reuben S.
Matsuo, Hiroshi
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyDocument Type
Journal ArticlePublication Date
2015-06-01Keywords
Cytidine DeaminaseDNA Mutational Analysis
Humans
Magnetic Resonance Spectroscopy
Models, Molecular
Mutant Proteins
Protein Binding
Protein Conformation
Protein Interaction Mapping
vif Gene Products, Human Immunodeficiency Virus
Biochemistry
Medicinal Chemistry and Pharmaceutics
Medicinal-Pharmaceutical Chemistry
Molecular Biology
Structural Biology
Virology
Metadata
Show full item recordAbstract
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.Source
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 siteDOI
10.1038/nsmb.3033Permanent Link to this Item
http://hdl.handle.net/20.500.14038/48905PubMed ID
25984970Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/nsmb.3033