Proteolytic elimination of N-myristoyl modifications by the Shigella virulence factor IpaJ

dc.contributor.authorBurnaevskiy, Nikolay
dc.contributor.authorFox, Thomas G.
dc.contributor.authorPlymire, Daniel A.
dc.contributor.authorErtelt, James M.
dc.contributor.authorWeigele, Bethany A.
dc.contributor.authorSelyunin, Andrey S.
dc.contributor.authorWay, Sing Sing
dc.contributor.authorPatrie, Steven M.
dc.contributor.authorAlto, Neal M.
dc.contributor.departmentPediatrics, School of Medicine
dc.date.accessioned2025-05-12T17:08:38Z
dc.date.available2025-05-12T17:08:38Z
dc.date.issued2013
dc.description.abstractProtein N-myristoylation is a 14-carbon fatty-acid modification that is conserved across eukaryotic species and occurs on nearly 1% of the cellular proteome. The ability of the myristoyl group to facilitate dynamic protein-protein and protein-membrane interactions (known as the myristoyl switch) makes it an essential feature of many signal transduction systems. Thus pathogenic strategies that facilitate protein demyristoylation would markedly alter the signalling landscape of infected host cells. Here we describe an irreversible mechanism of protein demyristoylation catalysed by invasion plasmid antigen J (IpaJ), a previously uncharacterized Shigella flexneri type III effector protein with cysteine protease activity. A yeast genetic screen for IpaJ substrates identified ADP-ribosylation factor (ARF)1p and ARF2p, small molecular mass GTPases that regulate cargo transport through the Golgi apparatus. Mass spectrometry showed that IpaJ cleaved the peptide bond between N-myristoylated glycine-2 and asparagine-3 of human ARF1, thereby providing a new mechanism for host secretory inhibition by a bacterial pathogen. We further demonstrate that IpaJ cleaves an array of N-myristoylated proteins involved in cellular growth, signal transduction, autophagasome maturation and organelle function. Taken together, these findings show a previously unrecognized pathogenic mechanism for the site-specific elimination of N-myristoyl protein modification.
dc.eprint.versionAuthor's manuscript
dc.identifier.citationBurnaevskiy N, Fox TG, Plymire DA, et al. Proteolytic elimination of N-myristoyl modifications by the Shigella virulence factor IpaJ. Nature. 2013;496(7443):106-109. doi:10.1038/nature12004
dc.identifier.urihttps://hdl.handle.net/1805/47985
dc.language.isoen_US
dc.publisherSpringer Nature
dc.relation.isversionof10.1038/nature12004
dc.relation.journalNature
dc.rightsPublisher Policy
dc.sourcePMC
dc.subjectBiocatalysis
dc.subjectListeria monocytogenes
dc.subjectSaccharomyces cerevisiae
dc.subjectVirulence
dc.titleProteolytic elimination of N-myristoyl modifications by the Shigella virulence factor IpaJ
dc.typeArticle
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