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

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 w...

Full description

Saved in:
Bibliographic Details
Published in:Nature communications 2014-09, Vol.5 (1), p.4919-4919, Article 4919
Main Authors: Thinon, Emmanuelle, Serwa, Remigiusz A., Broncel, Malgorzata, Brannigan, James A., Brassat, Ute, Wright, Megan H., Heal, William P., Wilkinson, Anthony J., Mann, David J., Tate, Edward W.
Format: Article
Language:English
Subjects:
631/92/458
631/92/475
82/58
82/80
96/2
Acyltransferases - genetics
Acyltransferases - metabolism
Crystallography, X-Ray
HeLa Cells
Humanities and Social Sciences
Humans
multidisciplinary
Myristic Acid - metabolism
Protein Processing, Post-Translational
Proteome - genetics
Proteome - metabolism
Science
Science (multidisciplinary)
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Protein N -myristoylation is a ubiquitous modification implicated in the regulation of multiple cellular processes. Here, Thinon et al. report the development of a general method to identify N -myristoylated proteins in human cells and identify over 100 endogenous post- and co-translational substrates of N -myristoyltransferase.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms5919