Evidence for a novel protease governing regulated intramembrane proteolysis and resistance to antimicrobial peptides in Bacillus subtilis.
Evidence is presented that the activation of the RNA polymerase sigma factor sigma(W) in Bacillus subtilis by regulated intramembrane proteolysis is governed by a novel, membrane-embedded protease. The sigma(W) factor is activated by proteolytic destruction of the membrane-bound anti-sigma(W) factor RsiW in response to antimicrobial peptides and other agents that damage the cell envelope. RsiW is destroyed by successive proteolytic events known as Site-1 and Site-2 cleavage. Site-2 cleavage is mediated by a member of the SpoIVFB-S2P family of intramembrane-acting metalloproteases, but the protease responsible for Site-1 cleavage was unknown. We have identified a previously uncharacterized, multipass membrane protein called PrsW (annotated YpdC) that is both necessary and sufficient (when artificially produced in an unrelated host bacterium) for Site-1 cleavage of RsiW. PrsW is a member of a widespread family of membrane proteins that includes at least one previously known protease. We identify residues important for proteolysis and a cluster of acidic residues involved in sensing antimicrobial peptides and cell envelope stress.
Ellermeier
Craig D
CD
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Losick
Richard
R
D019943:Amino Acid Substitution; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000502:physiology*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010447:Peptide Hydrolases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism; D014118:Toxins, Biological / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008565:Membrane Proteins; D010455:Peptides; C413458:SigW protein, Bacillus subtilis; D012808:Sigma Factor; D014118:Toxins, Biological; D010447:Peptide Hydrolases