Evidence of a Bacterial Receptor for Lysozyme: Binding of Lysozyme to the Anti-σ Factor RsiV Controls Activation of the ECF σ Factor σV

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. © 2014 hastie et al.