THE CHEMISTRY AND ENZYMOLOGY OF THE TYPE-I SIGNAL PEPTIDASES

The discovery that proteins exported from the cytoplasm are typically synthesized as larger precursors with cleavable signal peptides has fo cused interest on the peptidases that remove the signal peptides. Here , we review the membrane-bound peptidases dedicated to the processing of protein precursors that are found in the plasma membrane of prokary otes and the endoplasmic reticulum, the mitochondrial inner membrane, and the chloroplast thylakoidal membrane of eukaryotes. These peptidas es are termed type I signal (or leader) peptidases. They share the unu sual feature of being resistant to the general inhibitors of the four well-characterized peptidase classes. The eukaryotic and prokaryotic s ignal peptidases appear to belong to a single peptidase family. This r eview emphasizes the evolutionary concepts, current knowledge of the c atalytic mechanism, and substrate specificity requirements of the sign al peptidases.