title: Pilus chaperones represent a new type of protein-folding catalyst.
abstract: Adhesive type 1 pili from uropathogenic Escherichia coli strains have a crucial role during infection by mediating the attachment to and potentially the invasion of host tissue. These filamentous, highly oligomeric protein complexes are assembled by the 'chaperone-usher' pathway, in which the individual pilus subunits fold in the bacterial periplasm and form stoichiometric complexes with a periplasmic chaperone molecule that is essential for pilus assembly. The chaperone subsequently delivers the subunits to an assembly platform (usher) in the outer membrane, which mediates subunit assembly and translocation to the cell surface. Here we show that the periplasmic type 1 pilus chaperone FimC binds non-native pilus subunits and accelerates folding of the subunit FimG by 100-fold. Moreover, we find that the FimC-FimG complex is formed quantitatively and very rapidly when folding of FimG is initiated in the presence of both FimC and the assembly-competent subunit FimF, even though the FimC-FimG complex is thermodynamically less stable than the FimF-FimG complex. FimC thus represents a previously unknown type of protein-folding catalyst, and simultaneously acts as a kinetic trap preventing spontaneous subunit assembly in the periplasm.
authors.affiliation: Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule Hönggerberg, CH-8093 Zürich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Vetsch
authors.forename: Chasper
authors.initials: C
authors.lastname: Puorger
authors.forename: Thomas
authors.initials: T
authors.lastname: Spirig
authors.forename: Ulla
authors.initials: U
authors.lastname: Grauschopf
authors.forename: Eilika U
authors.initials: EU
authors.lastname: Weber-Ban
authors.forename: Rudi
authors.initials: R
authors.lastname: Glockshuber
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D004926:Escherichia coli / Q000737:chemistry / Q000378:metabolism* / Q000472:pathogenicity; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D036781:Fimbriae Proteins / Q000737:chemistry / Q000378:metabolism; D010861:Fimbriae, Bacterial / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D046911:Macromolecular Substances; D018832:Molecular Chaperones / Q000378:metabolism*; D019897:Periplasm / Q000737:chemistry / Q000378:metabolism; D017510:Protein Folding; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D046911:Macromolecular Substances; D018832:Molecular Chaperones; D021122:Protein Subunits; C489721:fimC protein, E coli; D036781:Fimbriae Proteins