Disentanglement of protease substrate repertoires.
Identification of protease substrates and detailed characterization of processed sites are essential for understanding the biological function of proteases. Because of inherent complexity reasons, this however remains a formidable analytical challenge, illustrated by the fact that the majority of the more than 500 human proteases are uncharacterized to date. Recently, in addition to conventional genetic and biochemical approaches, diverse quantitative peptide-centric proteomics approaches, some of which selectively recover N-terminal peptides, have emerged. These latter proteomic technologies in particular allow the identification of natural protease substrates and delineation of cleavage sites in a complex, natural background of thousands of different proteins. We here review current biochemical, genetic and proteomic methods for global analysis of substrates of proteases and discuss selected applications.
Van Damme
Petra
P
Department of Medical Protein Research, Flanders Interuniversity Institute for Biotechnology (VIB), B-9000 Ghent, Belgium.
Vandekerckhove
Joel
J
Gevaert
Kris
K
D000818:Animals; D006801:Humans; D008954:Models, Biological; D010447:Peptide Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D013379:Substrate Specificity
D010447:Peptide Hydrolases