Project description:The mammalian mitochondrial rhomboid protease PARL is a critical regulator of mitochondrial homeostasis through its cleavage of substrates such as PINK1, PGAM5, and Smac, which have roles in mitochondrial quality control and apoptosis. Here are the LC-MS/MS data of Multiplex substrate profiling results for mitochondrial PARL in support for the manuscript "Insights into the catalytic properties of the mitochondrial rhomboid protease PARL".
Project description:Multiplex substrate profiling by mass spectrometry obtained from the cleavage of Nf20S under presence of marizomib after time zero (T0, 4 replicates) and time 240minutes (T240, 4 replicates).
Project description:Proteases within the C1B hydrolase family are encoded by many organisms. We subjected a putative C1B-like cysteine protease secreted by the human gut commensal Parabacteroidetes distasonis to mass spectrometry-based substrate profiling to find preferred peptide substrates. The P. distasonis protease, we termed Pd_dinase, has a sequential di-aminopeptidase activity with strong specificity for N-terminal glycine residues. The homohexameric Pd_dinase structure in complex with an irreversible dipeptide inhibitor, based on the preferred cleavage sequence, uncovered unexpected active site features that govern the strict substrate preferences and differentiate this protease from members of the C1B and broader papain-like C1 proteases. Due to their increased glycine content, we subjected several human-produced gut antimicrobial peptides to Pd_dinase and showed robust proteolytic degradation. We posit that secretion of Pd_dinase into the extracellular milieu and inactivation of host-produced antimicrobial peptides permits gut colonization by P. distasonis.