title: Molecular mechanism of P pilus termination in uropathogenic Escherichia coli.
abstract: P pili are important adhesive fibres that are assembled by the conserved chaperone-usher pathway. During pilus assembly, the subunits are incorporated into the growing fibre by the donor-strand exchange mechanism, whereby the beta-strand of the chaperone, which complements the incomplete immunoglobulin fold of each subunit, is displaced by the amino-terminal extension of an incoming subunit in a zip-in-zip-out exchange process that is initiated at the P5 pocket, an exposed hydrophobic pocket in the groove of the subunit. In vivo, termination of P pilus growth requires a specialized subunit, PapH. Here, we show that PapH is incorporated at the base of the growing pilus, where it is unable to undergo donor-strand exchange. This inability is not due to a stronger PapD-PapH interaction, but to a lack of a P5 initiator pocket in the PapH structure, suggesting that PapH terminates pilus growth because it is lacking the initiation point by which donor-strand exchange proceeds.
authors.affiliation: Institute of Structural Molecular Biology, University College London, Birkbeck College, Malet Street, London WC1E 7HX, UK.
authors.forename: Denis
authors.initials: D
authors.lastname: Verger
authors.forename: Eric
authors.initials: E
authors.lastname: Miller
authors.forename: Han
authors.initials: H
authors.lastname: Remaut
authors.forename: Gabriel
authors.initials: G
authors.lastname: Waksman
authors.forename: Scott
authors.initials: S
authors.lastname: Hultgren
mesh_terms: D001422:Bacterial Adhesion; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010861:Fimbriae, Bacterial / Q000378:metabolism / Q000502:physiology*; D018832:Molecular Chaperones / Q000235:genetics / Q000502:physiology*; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D029968:Escherichia coli Proteins; D018832:Molecular Chaperones