Proteins are acylated by a variety of metabolites that regulates many important cellular pathways in all kingdoms of life. Acyl groups in cells can vary in structure from the smallest unit, acetate, to modified long-chain fatty acids, all of which can be activated and covalently attached to diverse amino acid side chains and consequently modulate protein function. For example, acetylation of Lys residues can alter the charge state of proteins and generate new recognition elements for protein–protein interactions. Alternatively, long-chain fatty-acylation targets proteins to membranes and enables spatial control of cell signalling. To facilitate the analysis of protein acylation in biology, acyl analogues bearing alkyne or azide tags have been developed that enable fluorescent imaging and proteomic profiling of modified proteins using bioorthogonal ligation methods. Herein, we summarize the currently available acylation chemical reporters and highlight their utility to discover and quantify the roles of protein acylation in biology.
- chemical proteomics
- chemical reporters
- post-translational modification
- protein acylation
Protein Acylation: from Mechanism to Drug Discovery: Held at the University of Edinburgh, U.K., 10–12 September 2014.
Abbreviations: ABE, acyl-biotin exchange; CoA, Coenzyme A; CuAAC, CuI-catalysed azide-alkyne cycloaddition; HDYOA, 15-hexadecynyloxyacetic acid; ICAT, isotope-coded affinity tag; IFITM3, Interferon-induced transmembrane protein 3; KAT, lysine acyltransferase; LC–MS/MS, liquid chromatography–tandem mass spectrometry; NMT, N-myristoyltransferase; 17-ODYA, 17-octadecynoic acid; RAC, resin-assisted capture; Shh, Sonic Hedgehog; SILAC, stable isotope labelling by amino acids in cell culture; SPAAC, strain-promoted alkyne-azide cycloaddition; TLR2, Toll-like receptor 2; Wnt, Wingless proteins
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