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

DOI: 10.1038/ncomms5919 DOI Help
PMID: 25255805 PMID Help

Authors: Emmanuelle Thinon (Department of Chemistry, Imperial College London) , Remigiusz A. Serwa (Department of Chemistry, Imperial College London) , Malgorzata Broncel (Department of Chemistry, Imperial College London) , James A. Brannigan (York Structural Biology Laboratory, Department of Chemistry) , Ute Brassat (Department of Chemistry, Imperial College London) , Megan H. Wright (Department of Chemistry, Imperial College London) , William P. Heal (Department of Chemistry, Imperial College London) , Anthony Wilkinson (York Structural Biology Laboratory, Department of Chemistry) , David J. Mann (Department of Life Sciences, Imperial College London) , Edward W. Tate (Department of Chemistry, Institute of Chemical Biology)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 5 , PAGES 465-468

State: Published (Approved)
Published: August 2014
Diamond Proposal Number(s): 1221

Open Access Open Access

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.

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography

Documents:
ncomms5919.pdf