Crystal structure of the DNA cytosine deaminase APOBEC3F: the catalytically active and HIV-1 Vif-binding domain

Structure. 2013 Jun 4;21(6):1042-50. doi: 10.1016/j.str.2013.04.010. Epub 2013 May 16.

Abstract

Human APOBEC3F is an antiretroviral single-strand DNA cytosine deaminase, susceptible to degradation by the HIV-1 protein Vif. In this study the crystal structure of the HIV Vif binding, catalytically active, C-terminal domain of APOBEC3F (A3F-CTD) was determined. The A3F-CTD shares structural motifs with portions of APOBEC3G-CTD, APOBEC3C, and APOBEC2. Residues identified to be critical for Vif-dependent degradation of APOBEC3F all fit within a predominantly negatively charged contiguous region on the surface of A3F-CTD. Specific sequence motifs, previously shown to play a role in Vif susceptibility and virion encapsidation, are conserved across APOBEC3s and between APOBEC3s and HIV-1 Vif. In this structure these motifs pack against each other at intermolecular interfaces, providing potential insights both into APOBEC3 oligomerization and Vif interactions.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Catalysis
  • Crystallography, X-Ray
  • Cytosine Deaminase / chemistry
  • Cytosine Deaminase / metabolism*
  • HIV-1 / metabolism*
  • Models, Molecular
  • Protein Conformation
  • vif Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • vif Gene Products, Human Immunodeficiency Virus
  • vif protein, Human immunodeficiency virus 1
  • APOBEC3F protein, human
  • Cytosine Deaminase