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Proteomics profiles of protein modifications

Histones are eukaryotic cell nuclei proteins that act as spools packing DNA into tight structural units. European scientists have studied post-synthetic protein modifications and their role in gene regulation.
Proteomics profiles of protein modifications
Eukaryotic genomes in cell nuclei are 40 000 times shorter than an unpacked molecule, thanks to histones. Cores and long tails of histone molecules can be covalently modified at several places. Histone post-translational modifications (PTMs) act in diverse processes such as gene regulation, DNA repair, mitosis and meiosis. PTMs of histones include methylation, acetylation, phosphorylation, ubiquitination and lipidation.

Application of chemical proteomics has resulted in groundbreaking insights into the chemistry and biology of PTMs. The aim of this EU-funded CHEMPROT-HLMS (Chemical proteomics for universal profiling of histone lysine malonylation and succinylation) project was to develop chemistry-based approaches for analysis of the lipidation (myristoylation and prenylation) involved in PTMs.

Investigators developed a new YnMyr probe (alkyne analogue of myristic acid) for chemical proteomics identification of N-myristoylated proteins. Large-scale quantitative proteomics experiments were carried out using different cell lines. Cells were analysed in normal conditions and after induction of apoptosis (cell death). Analysis of the proteomics data demonstrated significant differences in de novo myristoylation activity in proteomes in apoptotic cells.

In addition, new prenylation probes have been developed for PTM analysis in live cells. Applying these probes enabled quantification of modification in individual proteins in response to inhibition of the different prenyl transferases.

Current global drug development integrates drug discovery with systems biology. Thus, new methods developed by CHEMPROT-HLMS are expected to aid the profiling of drug candidates across biological networks.

Related information


Proteomics, histone post-translational modifications, CHEMPROT-HLMS, myristoylation, prenylation
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