Effects of inhibitors of membrane signal peptide peptidase on protein translocation into membrane vesicles.
The effect of the removal of signal peptides after cleavage of precursor molecules by the signal peptidase I was examined in an in vitro translocation system with Escherichia coli membrane vesicles. The translocation of periplasmic alkaline phosphatase precursors was significantly inhibited by the protease inhibitors antipain, elastatinal and leupeptin. Antipain and leupeptin enhanced the translocation of precursors of outer membrane protein OmpA, but inhibited the processing. However, antipain did not inhibit the processing of precursors mediated by signal peptidase I in the soluble form. Moreover, the inhibition by antipain was not due to the disruption of membrane integrity, but occurred during the process of protein translocation. Since these small peptide inhibitors are known to inhibit membrane protease IV, a signal peptide peptidase, these results suggest that the hydrolysis of signal peptides is an important step in the recycles of the overall translocation process, and that the prevention of degradation of signal peptides feedback inhibits the preceding steps in the translocation pathway.
Chen
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Department of Fine Structure, Boston Biomedical Research Institute, MA 02114.
Tai
P C
PC
D000469:Alkaline Phosphatase / Q000378:metabolism; D000976:Antipain / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology* / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D008565:Membrane Proteins; D009842:Oligopeptides / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D021382:Protein Sorting Signals / Q000378:metabolism*; D012697:Serine Endopeptidases
D001425:Bacterial Outer Membrane Proteins; D007976:Leupeptins; D008565:Membrane Proteins; D009842:Oligopeptides; D011480:Protease Inhibitors; D021382:Protein Sorting Signals; D000976:Antipain; D000469:Alkaline Phosphatase; D010450:Endopeptidases; D012697:Serine Endopeptidases; C026515:type I signal peptidase; C032854:leupeptin; C010718:elastatinal