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Nat Commun. 2014 Sep 26;5:4919. doi: 10.1038/ncomms5919.

Global profiling of co- and post-translationally N-myristoylated proteomes in human cells.

Author information

1
1] Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, UK [2] Department of Life Sciences, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
2
Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
3
York Structural Biology Laboratory, Department of Chemistry, University of York, York YO10 5DD, UK.
4
1] Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, UK [2] Department of Chemistry, Institute of Chemical Biology, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
5
1] Department of Life Sciences, Imperial College London, Exhibition Road, London SW7 2AZ, UK [2] Department of Chemistry, Institute of Chemical Biology, Imperial College London, Exhibition Road, London SW7 2AZ, UK.

Abstract

Protein N-myristoylation is a ubiquitous co- and post-translational modification that has been implicated in the development and progression of a range of human diseases. Here, we report the global N-myristoylated proteome in human cells determined using quantitative chemical proteomics combined with potent and specific human N-myristoyltransferase (NMT) inhibition. Global quantification of N-myristoylation during normal growth or apoptosis allowed the identification of >100 N-myristoylated proteins, >95% of which are identified for the first time at endogenous levels. Furthermore, quantitative dose response for inhibition of N-myristoylation is determined for >70 substrates simultaneously across the proteome. Small-molecule inhibition through a conserved substrate-binding pocket is also demonstrated by solving the crystal structures of inhibitor-bound NMT1 and NMT2. The presented data substantially expand the known repertoire of co- and post-translational N-myristoylation in addition to validating tools for the pharmacological inhibition of NMT in living cells.

PMID:
25255805
PMCID:
PMC4200515
DOI:
10.1038/ncomms5919
[Indexed for MEDLINE]
Free PMC Article

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