Evidence for a novel protease governing regulated intramembrane proteolysis and resistance to antimicrobial peptides in Bacillus subtilis

Craig D Ellermeier; Richard Losick

doi:10.1101/gad.1440606

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Evidence for a novel protease governing regulated intramembrane proteolysis and resistance to antimicrobial peptides in Bacillus subtilis

Journal article

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Evidence for a novel protease governing regulated intramembrane proteolysis and resistance to antimicrobial peptides in Bacillus subtilis

Craig D Ellermeier and Richard Losick

Genes & development, Vol.20(14), pp.1911-1922

07/15/2006

DOI: 10.1101/gad.1440606

PMCID: PMC1522089

PMID: 16816000

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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.

Sigma Factor - metabolism

Membrane Proteins - genetics

Peptide Hydrolases - genetics

Peptide Hydrolases - drug effects

Bacterial Proteins - genetics

Peptides - pharmacology

Bacterial Proteins - drug effects

Escherichia coli - genetics

Drug Resistance, Bacterial - physiology

Escherichia coli - metabolism

Membrane Proteins - drug effects

Bacterial Proteins - metabolism

Anti-Bacterial Agents - pharmacology

Cell Membrane - metabolism

Membrane Proteins - metabolism

Mutation

Sigma Factor - genetics

Bacillus subtilis - metabolism

Amino Acid Substitution

Bacillus subtilis - drug effects

Peptide Hydrolases - metabolism

Toxins, Biological - pharmacology

Details

Title: Subtitle: Evidence for a novel protease governing regulated intramembrane proteolysis and resistance to antimicrobial peptides in Bacillus subtilis
Creators: Craig D Ellermeier - Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Richard Losick
Resource Type: Journal article
Publication Details: Genes & development, Vol.20(14), pp.1911-1922
DOI: 10.1101/gad.1440606
PMID: 16816000
PMCID: PMC1522089
ISSN: 0890-9369
eISSN: 1549-5477
Grant note: R01 GM018568 / NIGMS NIH HHS R37 GM018568 / NIGMS NIH HHS GM18568 / NIGMS NIH HHS
Language: English
Date published: 07/15/2006
Academic Unit: Microbiology and Immunology
Record Identifier: 9984083269202771

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