Structure of the Vif-binding domain of the antiviral enzyme APOBEC3G.

Authors

Takahide Kouno, Biochemistry, Molecular Biology and Biophysics Department, Institute for Molecular Virology, University of Minnesota; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School
Elizabeth M Luengas, Biochemistry, Molecular Biology and Biophysics Department, Masonic Cancer Center, University of Minnesota
Megumi Shigematsu, Biochemistry, Molecular Biology and Biophysics Department, Institute for Molecular Virology, University of Minnesota; Department of Biochemistry and Molecular Biology, Thomas Jefferson UniversityFollow
Shivender M D Shandilya, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School
JingYing Zhang, Biochemistry, Molecular Biology and Biophysics Department, Institute for Molecular Virology, University of Minnesota; Department of Biochemistry and Molecular Biology, Thomas Jefferson University; Department of Physical Medicine and Rehabilitation, University of Minnesota
Luan Chen, Biochemistry, Molecular Biology and Biophysics Department, Institute for Molecular Virology, University of Minnesota; Department of Biochemistry and Molecular Biology, Thomas Jefferson University; Program in Computational Biology and Bioinformatics, Yale University
Mayuko Hara, Biochemistry, Molecular Biology and Biophysics Department, Institute for Molecular Virology, University of Minnesota; Department of Biochemistry and Molecular Biology, Thomas Jefferson University; Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka
Celia A Schiffer, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School
Reuben S Harris, Biochemistry, Molecular Biology and Biophysics Department, Masonic Cancer Center, University of Minnesota
Hiroshi Matsuo, Biochemistry, Molecular Biology and Biophysics Department, Institute for Molecular Virology, University of Minnesota

Document Type

Article

Publication Date

6-3-2015

Comments

This article has been peer reviewed. It was published in: Nature Structural and Molecular Biology.

Volume 22, Issue 6, 3 June 2015, Pages 485-491.

The published version is available at DOI: 10.1038/nsmb.3033

Copyright © 2015 Nature America, Inc.

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.

Recommended Citation

Kouno, Takahide; Luengas, Elizabeth M; Shigematsu, Megumi; Shandilya, Shivender M D; Zhang, JingYing; Chen, Luan; Hara, Mayuko; Schiffer, Celia A; Harris, Reuben S; and Matsuo, Hiroshi, "Structure of the Vif-binding domain of the antiviral enzyme APOBEC3G." (2015). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 93.
https://jdc.jefferson.edu/bmpfp/93

PubMed ID

25984970