title: Inositol pyrophosphate mediated pyrophosphorylation of AP3B1 regulates HIV-1 Gag release.
abstract: High-energy inositol pyrophosphates, such as IP(7) (diphosphoinositol pentakisphosphate), can directly donate a beta-phosphate to a prephosphorylated serine residue generating pyrophosphorylated proteins. Here, we show that the beta subunit of AP-3, a clathrin-associated protein complex required for HIV-1 release, is a target of IP(7)-mediated pyrophosphorylation. We have identified Kif3A, a motor protein of the kinesin superfamily, as an AP3B1-binding partner and demonstrate that Kif3A, like the AP-3 complex, is involved in an intracellular process required for HIV-1 Gag release. Importantly, IP(7)-mediated pyrophosphorylation of AP3B1 modulates the interaction with Kif3A and, as a consequence, affects the release of HIV-1 virus-like particles. This study identifies a cellular process that is regulated by IP(7)-mediated pyrophosphorylation.
authors.affiliation: Cell Biology Unit, Medical Research Council Laboratory for Molecular Cell Biology, and Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom.
authors.forename: Cristina
authors.initials: C
authors.lastname: Azevedo
authors.forename: Adam
authors.initials: A
authors.lastname: Burton
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Ruiz-Mateos
authors.forename: Mark
authors.initials: M
authors.lastname: Marsh
authors.forename: Adolfo
authors.initials: A
authors.lastname: Saiardi
mesh_terms: D033963:Adaptor Protein Complex 3 / Q000378:metabolism*; D033966:Adaptor Protein Complex beta Subunits / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport; D011756:Diphosphates / Q000378:metabolism*; D015683:Gene Products, gag / Q000378:metabolism*; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism*; D016547:Kinesins / Q000378:metabolism; D010766:Phosphorylation
chemical_list: C439973:AP3B1 protein, human; D033963:Adaptor Protein Complex 3; D033966:Adaptor Protein Complex beta Subunits; D033942:Adaptor Proteins, Vesicular Transport; D011756:Diphosphates; D015683:Gene Products, gag; D007295:Inositol Phosphates; C087415:KIF3A protein, human; C079849:1-diphosphoinositol pentakisphosphate; D016547:Kinesins