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Publication Detail
Inositol pyrophosphate mediated pyrophosphorylation of AP3B1 regulates HIV-1 Gag release.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Azevedo C, Burton A, Ruiz-Mateos E, Marsh M, Saiardi A
  • Publication date:
  • Pagination:
    21161, 21166
  • Journal:
    Proc Natl Acad Sci U S A
  • Volume:
  • Issue:
  • Status:
  • Country:
    United States
  • PII:
  • Language:
  • Keywords:
    Adaptor Protein Complex 3, Adaptor Protein Complex beta Subunits, Adaptor Proteins, Vesicular Transport, Diphosphates, Gene Products, gag, HIV-1, Humans, Inositol Phosphates, Kinesin, Phosphorylation
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.
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