title: PapD-like chaperones provide the missing information for folding of pilin proteins.
abstract: A fundamental question in molecular biology is how proteins fold into domains that can serve as assembly modules for building up large macromolecular structures. The biogenesis of pili on the surface of Gram-negative bacteria requires the orchestration of a complex process that includes protein synthesis, folding via small chaperones, secretion, and assembly. The results presented here support the hypothesis that pilus subunit folding and biogenesis proceed via mechanisms termed donor strand complementation and donor strand exchange. Here we show that the steric information necessary for pilus subunit folding is not contained in one polypeptide sequence. Rather, the missing information is transiently donated by a strand of a small chaperone to allow folding. Providing the missing information for folding, via a 13-amino acid peptide extension to the C-terminal end of a pilus subunit, resulted in the production of a protein that no longer required the chaperone to fold. This mechanism of small periplasmic chaperone function described here deviates from classical hsp60 chaperone-assisted folding.
authors.affiliation: Departments of Molecular Microbiology and Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Barnhart
authors.forename: J S
authors.initials: JS
authors.lastname: Pinkner
authors.forename: G E
authors.initials: GE
authors.lastname: Soto
authors.forename: F G
authors.initials: FG
authors.lastname: Sauer
authors.forename: S
authors.initials: S
authors.lastname: Langermann
authors.forename: G
authors.initials: G
authors.lastname: Waksman
authors.forename: C
authors.initials: C
authors.lastname: Frieden
authors.forename: S J
authors.initials: SJ
authors.lastname: Hultgren
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism; D018830:Adhesins, Escherichia coli; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002942:Circular Dichroism; D003198:Computer Simulation; D010450:Endopeptidases; D029968:Escherichia coli Proteins; D036781:Fimbriae Proteins; D010861:Fimbriae, Bacterial / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000378:metabolism; D006388:Hemagglutinins / Q000032:analysis; D008565:Membrane Proteins / Q000378:metabolism*; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000378:metabolism*; D019897:Periplasm / Q000378:metabolism; D033903:Periplasmic Proteins; D011489:Protein Denaturation; D017510:Protein Folding; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D018830:Adhesins, Escherichia coli; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D006388:Hemagglutinins; D008565:Membrane Proteins; D018832:Molecular Chaperones; C084330:PapD protein, E coli; D033903:Periplasmic Proteins; D011994:Recombinant Proteins; C058769:fimH protein, E coli; D036781:Fimbriae Proteins; D010450:Endopeptidases; C067127:prepilin peptidase protein, Bacteria