title: Membrane-associated DegP in Bordetella chaperones a repeat-rich secretory protein.
abstract: The chaperone/protease DegP belongs to the HtrA superfamily and is involved in protein quality control in the periplasm of Gram-negative bacteria. In Escherichia coli, typical substrates are unfolded or misfolded globular proteins that trigger the rearrangement of inactive DegP hexamers into substrate-sequestering 12- or 24-mers 'cages' for refolding or degradation. In Bordetella pertussis, DegP(Bp) facilitates, in addition, the secretion of FHA, a long β-helical adhesin that passes through the periplasm in an extended conformation. We show that DegP(Bp) exists as soluble trimers and as a membrane-associated form. Different substrates interact differently with the distinct forms of DegP(Bp), and membrane-associated DegP(Bp) has high affinity for non-native FHA. Unlike more globular substrates, FHA does not efficiently mediate rearrangement of trimers into proteolytically active, short-lived dodecamers. In contrast to these dodecamers, membrane-associated DegP(Bp) is not committed to substrate degradation, although it is proteolytically competent. In B. pertussis, membrane-associated DegP(Bp) thus represents a specific functional form serving as a holding chaperone for client proteins including FHA. If FHA secretion is impaired, membrane-associated DegP(Bp) participates in its degradation. This form of DegP(Bp) is appropriate to handle substrates unsuitable to be sequestered in cages or non-folded, secretory proteins that must not be degraded.
authors.affiliation: Inserm U1019, Center for Infection and Immunity of Lille, F-59019 Lille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Baud
authors.forename: Irina
authors.initials: I
authors.lastname: Gutsche
authors.forename: Eve
authors.initials: E
authors.lastname: Willery
authors.forename: Diane
authors.initials: D
authors.lastname: de Paepe
authors.forename: Hervé
authors.initials: H
authors.lastname: Drobecq
authors.forename: Martine
authors.initials: M
authors.lastname: Gilleron
authors.forename: Camille
authors.initials: C
authors.lastname: Locht
authors.forename: Marc
authors.initials: M
authors.lastname: Jamin
authors.forename: Françoise
authors.initials: F
authors.lastname: Jacob-Dubuisson
mesh_terms: D001886:Bordetella pertussis / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D033903:Periplasmic Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D010566:Virulence Factors, Bordetella / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D033903:Periplasmic Proteins; D010566:Virulence Factors, Bordetella; C061682:DegP protease; D012697:Serine Endopeptidases