Myristoylome profiling reveals a concerted mechanism of ARF GTPase deacylation by the bacterial protease IpaJ

Nikolay Burnaevskiy, Tao Peng, L. Evan Reddick, Howard C. Hang, Neal M. Alto

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

N-myristoylation is an essential fatty acid modification that governs the localization and activity of cell signaling enzymes, architectural proteins, and immune regulatory factors. Despite its importance in health and disease, there are currently no methods for reversing protein myristoylation invivo. Recently, the Shigella flexneri protease IpaJ was found to cleave myristoylated glycine of eukaryotic proteins, yet the discriminatory mechanisms of substrate selection required for targeted demyristoylation have not yet been evaluated. Here, we performed global myristoylome profiling of cells treated with IpaJ under distinct physiological conditions. The protease is highly promiscuous among diverse N-myristoylated proteins invitro but is remarkably specific to Golgi-associated ARF/ARL family GTPases during Shigella infection. Reconstitution studies revealed a mechanistic framework for substrate discrimination based on IpaJ's function as a GTPase "effector" of bacterial origin. We now propose a concerted model for IpaJ function that highlights its potential for programmable demyristoylation invivo.

Original languageEnglish (US)
Pages (from-to)110-122
Number of pages13
JournalMolecular cell
Volume58
Issue number1
DOIs
StatePublished - Apr 2 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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