Article abstract
Nature Structural & Molecular Biology 15, 1184 - 1191 (2008)
Published online: 5 October 2008 | doi:10.1038/nsmb.1497
Phosphorylation of APOBEC3G by protein kinase A regulates its interaction with HIV-1 Vif
Kotaro Shirakawa1,2, Akifumi Takaori-Kondo1, Masaru Yokoyama3, Taisuke Izumi1, Masashi Matsui1, Katsuhiro Io1, Toshihiro Sato4, Hironori Sato3 & Takashi Uchiyama1
Abstract
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.
- Japanese Foundation for AIDS Prevention, 1-3-12 Misaki-cho, Chiyoda-ku, Tokyo 101-0061, Japan.
- Laboratory of Viral Genomics, Center for Pathogen Genomics, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
- Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
Correspondence to: Akifumi Takaori-Kondo1 e-mail: atakaori@kuhp.kyoto-u.ac.jp
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