title: The extracytoplasmic adaptor protein CpxP is degraded with substrate by DegP.
abstract: In Escherichia coli, the CpxR/A two-component system senses various types of extracytoplasmic stresses and responds by activating the expression of genes encoding periplasmic protein folding and trafficking factors that clear such stresses to ensure the organism's survival. The cpxP gene encodes a small, stress-combative periplasmic protein and is the most strongly induced member of the Cpx regulon. We demonstrate that the Cpx stress response suppresses the toxicity associated with two misfolded proteins derived from the P pilus of uropathogenic E. coli and that mutations in either cpxP or the gene for the periplasmic protease DegP prevent suppression by preventing the degradation of these proteins. Strikingly, the presence of a periplasmic misfolded protein substrate significantly enhances the proteolysis of CpxP by DegP. Our data suggest that CpxP functions as a periplasmic adaptor protein that is required for the effective proteolysis of a subset of misfolded substrates by the DegP protease.
authors.affiliation: Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Washington Road, Princeton, NJ 08544, USA.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Isaac
authors.forename: Jerome S
authors.initials: JS
authors.lastname: Pinkner
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Hultgren
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Silhavy
mesh_terms: D018830:Adhesins, Escherichia coli / Q000378:metabolism; D003593:Cytoplasm; D004926:Escherichia coli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism* / Q000494:pharmacology; D036781:Fimbriae Proteins / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism* / Q000494:pharmacology; D033903:Periplasmic Proteins / Q000378:metabolism*; D017510:Protein Folding; D006180:Proton-Translocating ATPases / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D018830:Adhesins, Escherichia coli; C491730:CpxP protein, E coli; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; C092426:PapG protein, E coli; D033903:Periplasmic Proteins; D036781:Fimbriae Proteins; C061682:DegP protease; D012697:Serine Endopeptidases; D006180:Proton-Translocating ATPases; C101709:AtpH protein, E coli