The metalloprotease of Listeria monocytogenes is activated by intramolecular autocatalysis.
The metalloprotease (Mpl) of Listeria monocytogenes is a thermolysin-like protease that mediates the maturation of a broad-range phospholipase C, whose function contributes to the ability of this food-borne bacterial pathogen to survive intracellularly. Mpl is made as a proprotein that undergoes maturation by proteolytic cleavage of a large N-terminal prodomain. In this study, we identified the N terminus of mature Mpl and generated Mpl catalytic mutants to investigate the mechanism of Mpl maturation. We observed that Mpl activity was a prerequisite for maturation, suggesting a mechanism of autocatalysis. Furthermore, using a strain of L. monocytogenes expressing both the wild-type form and a catalytic mutant form of Mpl simultaneously, we determined that in vivo maturation of Mpl occurs exclusively by an intramolecular autocatalysis mechanism.
Bitar
Alan Pavinski
AP
Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, USA.
Cao
Min
M
Marquis
Hélène
H
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000378:metabolism; D002384:Catalysis; D017931:DNA Primers; D004789:Enzyme Activation; D005838:Genotype; D007700:Kinetics; D008089:Listeria monocytogenes / Q000201:enzymology* / Q000235:genetics; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry; D011994:Recombinant Proteins / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D001426:Bacterial Proteins; D017931:DNA Primers; D010446:Peptide Fragments; D011994:Recombinant Proteins; D010738:Type C Phospholipases; D045726:Metalloproteases