Crystal Structure of the DNA Cytosine Deaminase APOBEC3F: The Catalytically Active and HIV-1 Vif-Binding Domain
Department of Pediatrics; Department of Biochemistry and Molecular Pharmacology
Cytosine Deaminase; vif Gene Products, Human Immunodeficiency Virus
Biochemistry, Biophysics, and Structural Biology | Immunology and Infectious Disease
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.
DOI of Published Version
Structure. 2013 Jun 4;21(6):1042-50. doi: 10.1016/j.str.2013.04.010. Link to article on publisher's site
Structure (London, England : 1993)
Bohn, Markus-Frederik; Shandilya, Shivender M. D.; Albin, John S.; Kouno, Takahide; Anderson, Brett D.; McDougle, Rebecca M.; Carpenter, Michael A.; Rathore, Anurag; Evans, Leah; Davis, Ahkillah N.; Zhang, JingYing; Lu, Yongjian; Somasundaran, Mohan; Matsuo, Hiroshi; Harris, Reuben S.; and Schiffer, Celia A., "Crystal Structure of the DNA Cytosine Deaminase APOBEC3F: The Catalytically Active and HIV-1 Vif-Binding Domain" (2013). University of Massachusetts Medical School Faculty Publications. 22.