title: Dynamic interaction between the CpxA sensor kinase and the periplasmic accessory protein CpxP mediates signal recognition in E. coli.
abstract: Two-component systems, consisting of an inner membrane sensor kinase and a cytosolic response regulator, allow bacteria to respond to changes in the environment. Some two-component systems are additionally orchestrated by an accessory protein that integrates additional signals. It is assumed that spatial and temporal interaction between an accessory protein and a sensor kinase modifies the activity of a two-component system. However, for most accessory proteins located in the bacterial envelope the mechanistic details remain unclear. Here, we analyzed the interaction between the periplasmic accessory protein CpxP and the sensor kinase CpxA in Escherichia coli in dependency of three specific stimuli. The Cpx two-component system responds to envelope stress and plays a pivotal role for the quality control of multisubunit envelope structures, including type three secretion systems and pili of different pathogens. In unstressed cells, CpxP shuts off the Cpx response by a yet unknown mechanism. We show for the first time the physical interaction between CpxP and CpxA in unstressed cells using bacterial two-hybrid system and membrane-Strep-tagged protein interaction experiments. In addition, we demonstrate that a high salt concentration and the misfolded pilus subunit PapE displace CpxP from the sensor kinase CpxA in vivo. Overall, this study provides clear evidence that CpxP modulates the activity of the Cpx system by dynamic interaction with CpxA in response to specific stresses.
authors.affiliation: University of Osnabrück, FB5, Molecular Microbiology, Osnabrück, Germany.
authors.forename: Karolin
authors.initials: K
authors.lastname: Tschauner
authors.affiliation: University of Osnabrück, FB5, Molecular Microbiology, Osnabrück, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Hörnschemeyer
authors.affiliation: Humboldt University Berlin, Department of Biology, Bacterial Physiology, Berlin, Germany.
authors.forename: Volker Steffen
authors.initials: VS
authors.lastname: Müller
authors.affiliation: University of Osnabrück, FB5, Molecular Microbiology, Osnabrück, Germany; Humboldt University Berlin, Department of Biology, Bacterial Physiology, Berlin, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hunke
mesh_terms: D058947:Bacterial Secretion Systems / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D010861:Fimbriae, Bacterial / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009997:Osmotic Pressure; D019897:Periplasm / Q000378:metabolism*; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D058947:Bacterial Secretion Systems; C491730:CpxP protein, E coli; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D011494:Protein Kinases; C490475:CpxA protein, E coli; D006180:Proton-Translocating ATPases; C101709:AtpH protein, E coli