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 σ factor σW in Bacillus subtilis by regulated intramembrane proteolysis is governed by a novel, membrane-embedded protease. The σW factor is activated by proteolytic destruction of the membrane-bound anti-σW 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.
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↵1 Corresponding author.
↵1 E-MAIL losick{at}mcb.harvard.edu; FAX (617) 496-4642.
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Supplemental material is available at http://www.genesdev.org.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.1440606
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- Received April 14, 2006.
- Accepted May 30, 2006.
- Copyright © 2006, Cold Spring Harbor Laboratory Press