Activity-Based Protein Profiling of Serine Proteases in Immune Cells
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(2020) 68:23
REVIEW
Activity‑Based Protein Profiling of Serine Proteases in Immune Cells Jan Pascal Kahler1 · Roeland Vanhoutte1 · Steven H. L. Verhelst1,2 Received: 31 October 2019 / Accepted: 11 June 2020 © L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2020
Abstract Multiple types of immune cells utilize serine proteases in their mechanisms of defense against pathogens or altered host cells. Dysregulation of the serine protease activity from these cells underlies different diseases. In the past, the technique of activity-based protein profiling proved to be especially useful for the study of proteases, and various studies have used smallmolecule activity-based probes to covalently label and detect serine proteases from immune cells. In this review, we give an overview of the different activity-based probes that have been designed for serine proteases and how their selectivity can be steered. We also discuss how these have been utilized in the detection of various serine proteases from immune cells by different analysis methods (gel electrophoresis, microscopy and flow cytometry) and what biological insights these studies have produced. Overall, activity-based protein profiling has the potential to address functional aspects of serine proteases in the immune system and future efforts may bring translation into clinical application. Keywords Activity-based probes · Cathepsin G · Covalent protease inhibitors · Neutrophil elastase Abbreviations ABP Activity-based probe ABPP Activity-based protein profiling APC Antigen-presenting cell CatG Cathepsin G CTL Cytotoxic T lymphocyte DCI 3,4-Dichloroisocoumarin ET Extracellular trap FRET Fluorescence resonance energy transfer Grz Granzyme HyCoSuL Hybrid combinatorial substrate library LF Lactoferrin MHC-I Major histocompatibility complex, Class I MHC-II Major histocompatibility complex, Class II NE Neutrophil elastase NET Neutrophil extracellular trap NETosis Form of cell death with neutrophil extracellular trap formation NK cell Natural killer cell NSP Neutrophil serine protease * Steven H. L. Verhelst [email protected]; [email protected] 1
Laboratory of Chemical Biology, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
Leibniz Institute for Analytical Sciences ISAS, E.V., Dortmund, Germany
2
NSP4 Neutrophil serine protease 4 PBMCs Peripheral blood mononuclear cells PMA Phorbol myristate acetate PML Polymorphonuclear leukocyte PPE Porcine pancreatic elastase PR3 Proteinase 3 PS-SCL Positional scanning synthetic combinatorial library qABP Quenched fluorescent activity-based probe SP Serine protease
Introduction Proteases are peptide-bond cleaving enzymes that make up approximately 2% of the human genome. They are divided into seven different groups based on their catalytic mechanism (Rawlings et al. 2018). Serine proteases (SPs) are the most abundant ones, and the majority belongs to the socalled S1 family, whose primary specificity is determined by the P1 po
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