Phosphorylation of APOBEC3G by protein kinase A regulates its interaction with HIV-1 Vif.
Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G, referred to here as A3G) is a potent antiretroviral host factor against human immunodeficiency virus type 1 (HIV-1). HIV-1 viral infectivity factor (Vif) counteracts A3G by promoting its degradation via the ubiquitin-proteasome pathway. Recent studies demonstrated that protein kinase A (PKA) phosphorylates activation-induced deaminase (AID), another member of the APOBEC3 family. A3G has two putative PKA phosphorylation residues. Here we show that PKA binds and specifically phosphorylates A3G at Thr32 in vitro and in vivo. This phosphorylation event reduces the binding of A3G to Vif and its subsequent ubiquitination and degradation, and thus promotes A3G antiviral activity. Computer-assisted structural modeling and mutagenesis studies suggest that the interaction between A3G Thr32 and Arg24 is crucial for interaction with Vif. These data imply that PKA-mediated phosphorylation of A3G can regulate the interaction between A3G and Vif.
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaracho, Sakyo-ku, Kyoto 606-8507, Japan.
Kotaro
K
Shirakawa
Akifumi
A
Takaori-Kondo
Masaru
M
Yokoyama
Taisuke
T
Izumi
Masashi
M
Matsui
Katsuhiro
K
Io
Toshihiro
T
Sato
Hironori
H
Sato
Takashi
T
Uchiyama
D000071480:APOBEC-3G Deaminase; D001120:Arginine / Q000378:metabolism; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003564:Cytidine Deaminase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016346:Gene Products, vif / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D014771:Virion / Q000378:metabolism
D016346:Gene Products, vif; D011993:Recombinant Fusion Proteins; D013912:Threonine; D001120:Arginine; D017868:Cyclic AMP-Dependent Protein Kinases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase