4.8 Article

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

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NATL ACAD SCIENCES
DOI: 10.1073/pnas.0909176106

关键词

phosphorylation; trafficking; kinesin

资金

  1. Medical Research Council (MRC)
  2. European Union (EU) Marie Curie through Institutional Research [014827]
  3. Fondo de Investigacio n Sanitaria [CD08/00172]
  4. Redes Tema ticas de Investigacio n Cooperativa [RD06/0006/0021]
  5. MRC [MC_U122680443, MC_U122665002] Funding Source: UKRI
  6. Medical Research Council [MC_U122665002, MC_U122680443] Funding Source: researchfish

向作者/读者索取更多资源

High-energy inositol pyrophosphates, such as IP7 (diphosphoinositol pentakisphosphate), can directly donate 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 IP7-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, IP7-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 IP7-mediated pyrophosphorylation.

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