The Prc and <scp>RseP</scp> proteases control bacterial cell‐surface signalling activity

<jats:title>Summary</jats:title><jats:p>Extracytoplasmic function (<jats:styled-content style="fixed-case">ECF</jats:styled-content>) sigma factors play a key role in the regulation of vital functions in the bacterial response to the environment. In Gram‐negative bacteria, activity of these sigma factors is often controlled by cell‐surface signalling (<jats:styled-content style="fixed-case">CSS</jats:styled-content>), a regulatory system that also involves an outer membrane receptor and a transmembrane anti‐sigma factor. To get more insight into the molecular mechanism behind <jats:styled-content style="fixed-case">CSS</jats:styled-content> regulation, we have focused on the unique Iut system of <jats:italic>Pseudomonas putida</jats:italic>. This system contains a hybrid protein containing both a cytoplasmic <jats:styled-content style="fixed-case">ECF</jats:styled-content> sigma domain and a periplasmic anti‐sigma domain, apparently leading to a permanent interaction between the sigma and anti‐sigma factor. We show that the Iut <jats:styled-content style="fixed-case">ECF</jats:styled-content> sigma factor regulates the response to aerobactin under iron deficiency conditions and is activated by a proteolytic pathway that involves the sequential action of two proteases: <jats:styled-content style="fixed-case">Prc</jats:styled-content>, which removes the periplasmic anti‐sigma domain, and <jats:styled-content style="fixed-case">RseP</jats:styled-content>, which subsequently removes the transmembrane domain and thereby generates the <jats:styled-content style="fixed-case">ECF</jats:styled-content> active transcriptional form. We furthermore demonstrate the role of these proteases in the regulation of classical <jats:styled-content style="fixed-case">CSS</jats:styled-content> systems in which the sigma and anti‐sigma factors are two different proteins.</jats:p>