Evidence of a bacterial receptor for lysozyme: binding of lysozyme to the anti-σ factor RsiV controls activation of the ecf σ factor σV

• Published in: PLoS genetics Vol. 10; no. 10; p. e1004643
• Main Authors: Hastie, Jessica L, Williams, Kyle B, Sepúlveda, Carolina, Houtman, Jon C, Forest, Katrina T, Ellermeier, Craig D
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-10-2014; Public Library of Science (PLoS)
• Subjects: Bacillus subtilis - genetics; Bacillus subtilis - metabolism; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biology and Life Sciences; Calorimetry - methods; Clostridioides difficile - metabolism; Endopeptidases - metabolism; Enterococcus faecalis - metabolism; Gene Expression Regulation, Bacterial; Medicine and Health Sciences; Membrane Proteins - genetics; Membrane Proteins - metabolism; Muramidase - genetics; Muramidase - metabolism; Proprotein Convertases - genetics; Proprotein Convertases - metabolism; Research and Analysis Methods; Serine Endopeptidases - genetics; Serine Endopeptidases - metabolism; Sigma Factor - genetics; Sigma Factor - metabolism
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1004643

σ factors endow RNA polymerase with promoter specificity in bacteria. Extra-Cytoplasmic Function (ECF) σ factors represent the largest and most diverse family of σ factors. Most ECF σ factors must be activated in response to an external signal. One mechanism of activation is the stepwise proteolytic destruction of an anti-σ factor via Regulated Intramembrane Proteolysis (RIP). In most cases, the site-1 protease required to initiate the RIP process directly senses the signal. Here we report a new mechanism in which the anti-σ factor rather than the site-1 protease is the sensor. We provide evidence suggesting that the anti-σ factor RsiV is the bacterial receptor for the innate immune defense enzyme, lysozyme. The site-1 cleavage site is similar to the recognition site of signal peptidase and cleavage at this site is required for σV activation in Bacillus subtilis. We reconstitute site-1 cleavage in vitro and demonstrate that it requires both signal peptidase and lysozyme. We demonstrate that the anti-σ factor RsiV directly binds to lysozyme and muramidase activity is not required for σV activation. We propose a model in which the binding of lysozyme to RsiV activates RsiV for signal peptidase cleavage at site-1, initiating proteolytic destruction of RsiV and activation of σV. This suggests a novel mechanism in which conformational change in a substrate controls the cleavage susceptibility for signal peptidase. Thus, unlike other ECF σ factors which require regulated intramembrane proteolysis for activation, the sensor for σV activation is not the site-1 protease but the anti-σ factor.