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

作者：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^*

来源：Nature Communications, 2014, 5(1): 4919.

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 4100 N-myristoylated proteins, 495% of which are identified for the first time at endogenous levels. Furthermore, quantitative dose response for inhibition of N-myristoylation is determined for 470 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.

• 出版日期2014-9