title: Crystal structure of the DNA cytosine deaminase APOBEC3F: the catalytically active and HIV-1 Vif-binding domain.
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.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Markus-Frederik
authors.initials: MF
authors.lastname: Bohn
authors.forename: Shivender M D
authors.initials: SM
authors.lastname: Shandilya
authors.forename: John S
authors.initials: JS
authors.lastname: Albin
authors.forename: Takahide
authors.initials: T
authors.lastname: Kouno
authors.forename: Brett D
authors.initials: BD
authors.lastname: Anderson
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: McDougle
authors.forename: Michael A
authors.initials: MA
authors.lastname: Carpenter
authors.forename: Anurag
authors.initials: A
authors.lastname: Rathore
authors.forename: Leah
authors.initials: L
authors.lastname: Evans
authors.forename: Ahkillah N
authors.initials: AN
authors.lastname: Davis
authors.forename: Jingying
authors.initials: J
authors.lastname: Zhang
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Lu
authors.forename: Mohan
authors.initials: M
authors.lastname: Somasundaran
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuo
authors.forename: Reuben S
authors.initials: RS
authors.lastname: Harris
authors.forename: Celia A
authors.initials: CA
authors.lastname: Schiffer
mesh_terms: D002384:Catalysis; D018360:Crystallography, X-Ray; D043525:Cytosine Deaminase / Q000737:chemistry / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; C492906:APOBEC3F protein, human; D043525:Cytosine Deaminase