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

Markus Frederik Bohn, Shivender M.D. Shandilya, John S. Albin, Takahide Kouno, Brett D. Anderson, Rebecca M. McDougle, Michael A. Carpenter, Anurag Rathore, Leah Evans, Ahkillah N. Davis, Jingying Zhang, Yongjian Lu, Mohan Somasundaran, Hiroshi Matsuo, Reuben S. Harris, Celia A. Schiffer

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1042-1050
Number of pages9
JournalStructure
Volume21
Issue number6
DOIs
StatePublished - Jun 4 2013

Bibliographical note

Funding Information:
This work was supported by National Institute of General Medical Sciences P01 GM091743. Drs. Nese Kurt Yilmaz and William Royer are thanked for their editorial and crystallographic support, respectively. Dr. Gang Han is thanked for the generous use of the Zetasizer Nano instrument to collect DLS data. X-ray diffraction data were collected at the Advanced Photon Source at sector 23-ID-B GM/CA-CAT, supported by the National Cancer Institute (Y1-CO-1020) and the National Institute of General Medical Sciences (Y1-GM-1104).

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