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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.

SUBMITTER: Azevedo C

PROVIDER: S-EPMC2795533 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Inositol pyrophosphate mediated pyrophosphorylation of AP3B1 regulates HIV-1 Gag release.

Azevedo Cristina C Burton Adam A Ruiz-Mateos Ezequiel E Marsh Mark M Saiardi Adolfo A

Proceedings of the National Academy of Sciences of the United States of America 20091123 50

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 th ...[more]

PMID: 19934039

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