title: ZraP is a periplasmic molecular chaperone and a repressor of the zinc-responsive two-component regulator ZraSR.
abstract: The bacterial envelope is the interface with the surrounding environment and is consequently subjected to a barrage of noxious agents including a range of compounds with antimicrobial activity. The ESR (envelope stress response) pathways of enteric bacteria are critical for maintenance of the envelope against these antimicrobial agents. In the present study, we demonstrate that the periplasmic protein ZraP contributes to envelope homoeostasis and assign both chaperone and regulatory function to ZraP from Salmonella Typhimurium. The ZraP chaperone mechanism is catalytic and independent of ATP; the chaperone activity is dependent on the presence of zinc, which is shown to be responsible for the stabilization of an oligomeric ZraP complex. Furthermore, ZraP can act to repress the two-component regulatory system ZraSR, which itself is responsive to zinc concentrations. Through structural homology, ZraP is a member of the bacterial CpxP family of periplasmic proteins, which also consists of CpxP and Spy. We demonstrate environmental co-expression of the CpxP family and identify an important role for these proteins in Salmonella's defence against the cationic antimicrobial peptide polymyxin B.
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: Corinne
authors.initials: C
authors.lastname: Appia-Ayme
authors.forename: Andrea
authors.initials: A
authors.lastname: Hall
authors.forename: Elaine
authors.initials: E
authors.lastname: Patrick
authors.forename: Shiny
authors.initials: S
authors.lastname: Rajadurai
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Clarke
authors.forename: Gary
authors.initials: G
authors.lastname: Rowley
mesh_terms: D018360:Crystallography, X-Ray; D024881:Drug Resistance, Bacterial / Q000502:physiology; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D007211:Indoles / Q000494:pharmacology; D008565:Membrane Proteins / Q000096:biosynthesis; D018832:Molecular Chaperones / Q000378:metabolism*; D019897:Periplasm / Q000187:drug effects / Q000378:metabolism; D033903:Periplasmic Proteins / Q000096:biosynthesis / Q000378:metabolism*; D011112:Polymyxin B / Q000494:pharmacology; D012097:Repressor Proteins / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000235:genetics* / Q000378:metabolism; D015032:Zinc / Q000378:metabolism
chemical_list: C491730:CpxP protein, E coli; D029968:Escherichia coli Proteins; D007211:Indoles; D008565:Membrane Proteins; D018832:Molecular Chaperones; D033903:Periplasmic Proteins; D012097:Repressor Proteins; C104888:Spy protein, E coli; C114106:zraP protein, E coli; C030374:indole; D011112:Polymyxin B; D015032:Zinc