title: Evidence for a novel protease governing regulated intramembrane proteolysis and resistance to antimicrobial peptides in Bacillus subtilis.
abstract: 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.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Craig D
authors.initials: CD
authors.lastname: Ellermeier
authors.forename: Richard
authors.initials: R
authors.lastname: Losick
mesh_terms: 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
chemical_list: 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