title: The chaperone-assisted membrane release and folding pathway is sensed by two signal transduction systems.
abstract: The assembly of interactive protein subunits into extracellular structures, such as pilus fibers in the Enterobacteriaceae, is dependent on the activity of PapD-like periplasmic chaperones. The ability of PapD to undergo a beta zippering interaction with the hydrophobic C-terminus of pilus subunits facilitates their folding and release from the cytoplasmic membrane into the periplasm. In the absence of the chaperone, subunits remained tethered to the membrane and were driven off-pathway via non-productive interactions. These off-pathway reactions were detrimental to cell growth; wild-type growth was restored by co-expression of PapD. Subunit misfolding in the absence of PapD was sensed by two parallel pathways: the Cpx two-component signaling system and the sigma E modulatory pathway.
authors.affiliation: Department of Molecular Microbiology, Washington University Medical School, St Louis, MO 63110, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Jones
authors.forename: P N
authors.initials: PN
authors.lastname: Danese
authors.forename: J S
authors.initials: JS
authors.lastname: Pinkner
authors.forename: T J
authors.initials: TJ
authors.lastname: Silhavy
authors.forename: S J
authors.initials: SJ
authors.lastname: Hultgren
mesh_terms: D018830:Adhesins, Escherichia coli / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins; D036781:Fimbriae Proteins; D010861:Fimbriae, Bacterial / Q000378:metabolism*; D006360:Heat-Shock Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D033903:Periplasmic Proteins; D017510:Protein Folding; D011494:Protein Kinases; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D012808:Sigma Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013104:Spheroplasts; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D018830:Adhesins, Escherichia coli; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D018832:Molecular Chaperones; C084330:PapD protein, E coli; C092426:PapG protein, E coli; D033903:Periplasmic Proteins; D011993:Recombinant Fusion Proteins; D012808:Sigma Factor; D014157:Transcription Factors; C063202:sporulation-specific sigma factors; D036781:Fimbriae Proteins; C085504:CpxR protein, Bacteria; D011494:Protein Kinases; C490475:CpxA protein, E coli; C092472:CpxA protein, bacteria; C061682:DegP protease; D012697:Serine Endopeptidases