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