title: Crystal structures of APOBEC3G N-domain alone and its complex with DNA.
abstract: 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.
authors.affiliation: Genetic, Molecular and Cellular Biology Program, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.|Molecular and Computational Biology Program, Departments of Biological Sciences and Chemistry, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Molecular and Computational Biology Program, Departments of Biological Sciences and Chemistry, University of Southern California, Los Angeles, California 90089, USA.|Center of Excellence in NanoBiophysics, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Shu-Xing
authors.initials: SX
authors.lastname: Li
authors.affiliation: Molecular and Computational Biology Program, Departments of Biological Sciences and Chemistry, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Hanjing
authors.initials: H
authors.lastname: Yang
authors.affiliation: Genetic, Molecular and Cellular Biology Program, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.|Molecular and Computational Biology Program, Departments of Biological Sciences and Chemistry, University of Southern California, Los Angeles, California 90089, USA.|Center of Excellence in NanoBiophysics, University of Southern California, Los Angeles, California 90089, USA.|Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Xiaojiang S
authors.initials: XS
authors.lastname: Chen
mesh_terms: D000071480:APOBEC-3G Deaminase / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D000818:Animals; D018360:Crystallography, X-Ray; D004277:DNA, Single-Stranded / Q000737:chemistry*; D015497:HIV-1 / Q000235:genetics*; D011323:Primates; D011485:Protein Binding; D000072417:Protein Domains; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification; D013329:Structure-Activity Relationship; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D004277:DNA, Single-Stranded; D011994:Recombinant Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; D000071480:APOBEC-3G Deaminase