title: Structure of the periplasmic stress response protein CpxP.
abstract: CpxP is a novel bacterial periplasmic protein with no homologues of known function. In gram-negative enteric bacteria, CpxP is thought to interact with the two-component sensor kinase, CpxA, to inhibit induction of the Cpx envelope stress response in the absence of protein misfolding. CpxP has also been shown to facilitate DegP-mediated proteolysis of misfolded proteins. Six mutations that negate the ability of CpxP to function as a signaling protein are localized in or near two conserved LTXXQ motifs that define a class of proteins with similarity to CpxP, Pfam PF07813. To gain insight into how these mutations might affect CpxP signaling and/or proteolytic adaptor functions, the crystal structure of CpxP from Escherichia coli was determined to 2.85-Å resolution. The structure revealed an antiparallel dimer of intertwined α-helices with a highly basic concave surface. Each protomer consists of a long, hooked and bent hairpin fold, with the conserved LTXXQ motifs forming two diverging turns at one end. Biochemical studies demonstrated that CpxP maintains a dimeric state but may undergo a slight structural adjustment in response to the inducing cue, alkaline pH. Three of the six previously characterized cpxP loss-of-function mutations, M59T, Q55P, and Q128H, likely result from a destabilization of the protein fold, whereas the R60Q, D61E, and D61V mutations may alter intermolecular interactions.
authors.affiliation: Department of Biochemistry, School of Molecular and Systems Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Gina L
authors.initials: GL
authors.lastname: Thede
authors.forename: David C
authors.initials: DC
authors.lastname: Arthur
authors.forename: Ross A
authors.initials: RA
authors.lastname: Edwards
authors.forename: Daelynn R
authors.initials: DR
authors.lastname: Buelow
authors.forename: Julia L
authors.initials: JL
authors.lastname: Wong
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Raivio
authors.forename: J N Mark
authors.initials: JN
authors.lastname: Glover
mesh_terms: D020816:Amino Acid Motifs; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D015398:Signal Transduction; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: C491730:CpxP protein, E coli; D029968:Escherichia coli Proteins; D008565:Membrane Proteins