title: The APOBEC3C crystal structure and the interface for HIV-1 Vif binding.
abstract: The human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3, referred to as A3) proteins are cellular cytidine deaminases that potently restrict retrovirus replication. However, HIV-1 viral infectivity factor (Vif) counteracts the antiviral activity of most A3 proteins by targeting them for proteasomal degradation. To date, the structure of an A3 protein containing a Vif-binding interface has not been solved. Here, we report a high-resolution crystal structure of APOBEC3C and identify the HIV-1 Vif-interaction interface. Extensive structure-guided mutagenesis revealed the role of a shallow cavity composed of hydrophobic or negatively charged residues between the α2 and α3 helices. This region is distant from the DPD motif (residues 128-130) of APOBEC3G that participates in HIV-1 Vif interaction. These findings provide insight into Vif-A3 interactions and could lead to the development of new pharmacologic anti-HIV-1 compounds.
authors.affiliation: Clinical Research Center, Department of Infectious Diseases and Immunology, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kitamura
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ode
authors.forename: Masaaki
authors.initials: M
authors.lastname: Nakashima
authors.forename: Mayumi
authors.initials: M
authors.lastname: Imahashi
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Naganawa
authors.forename: Teppei
authors.initials: T
authors.lastname: Kurosawa
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yokomaku
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamane
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Watanabe
authors.forename: Atsuo
authors.initials: A
authors.lastname: Suzuki
authors.forename: Wataru
authors.initials: W
authors.lastname: Sugiura
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Iwatani
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D003564:Cytidine Deaminase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D043525:Cytosine Deaminase / Q000737:chemistry; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity; D006367:HeLa Cells / Q000821:virology; D006801:Humans; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D014771:Virion / Q000235:genetics; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / 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; C495795:APOBEC3C protein, human; C578087:APOBEC3D protein, human; D003564:Cytidine Deaminase