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

• Published in: Nature communications Vol. 5; no. 1; p. 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: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.09.2014; Nature Publishing Group; Nature Pub. Group
• 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)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms5919

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.