Crystal structures of APOBEC3G N-domain alone and its complex with DNA

• Published in: Nature communications 2016-08, Vol.7 (1), p.12193-12193, Article 12193
• Main Authors: Xiao, Xiao, Li, Shu-Xing, Yang, Hanjing, Chen, Xiaojiang S.
• Format: Article
• Language: English
• Subjects: 82/16; 82/80; 82/83; Acids; Crystal structure; Humanities and Social Sciences; Molecular weight; multidisciplinary; NMR; Nuclear magnetic resonance; Proteins; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms12193

APOBEC3G (A3G) is a potent restriction factor of HIV-1. The N-terminal domain of A3G (A3G-CD1) is responsible for oligomerization and nucleic acid binding, both of which are essential for anti-HIV activity. As a countermeasure, HIV-1 viral infectivity factor (Vif) binds A3G-CD1 to mediate A3G degradation. The structural basis for the functions of A3G-CD1 remains elusive. Here, we report the crystal structures of a primate A3G-CD1 (rA3G-CD1) alone and in complex with single-stranded DNA (ssDNA). rA3G-CD1 shares a conserved core structure with the previously determined catalytic APOBECs, but displays unique features for surface charge, dimerization and nucleic acid binding. Its co-crystal structure with ssDNA reveals how the conformations of loops and residues surrounding the Zn-coordinated centre (Zn-centre) change upon DNA binding. The dimerization interface of rA3G-CD1 is important for oligomerization, nucleic acid binding and Vif-mediated degradation. These findings elucidate the molecular basis of antiviral mechanism and HIV-Vif targeting of A3G. The N-terminal domain of APOBEC3G (A3G) is required for anti-HIV activity, HIV-1 viral infectivity factor (Vif) binds to this domain of A3G to mediate its degradation. Here, the authors use their crystal structures of this A3G domain alone and bound to single-stranded DNA to investigate the molecular details of this interaction.