title: Crystal structure of the FimD usher bound to its cognate FimC-FimH substrate.
abstract: Type 1 pili are the archetypal representative of a widespread class of adhesive multisubunit fibres in Gram-negative bacteria. During pilus assembly, subunits dock as chaperone-bound complexes to an usher, which catalyses their polymerization and mediates pilus translocation across the outer membrane. Here we report the crystal structure of the full-length FimD usher bound to the FimC-FimH chaperone-adhesin complex and that of the unbound form of the FimD translocation domain. The FimD-FimC-FimH structure shows FimH inserted inside the FimD 24-stranded β-barrel translocation channel. FimC-FimH is held in place through interactions with the two carboxy-terminal periplasmic domains of FimD, a binding mode confirmed in solution by electron paramagnetic resonance spectroscopy. To accommodate FimH, the usher plug domain is displaced from the barrel lumen to the periplasm, concomitant with a marked conformational change in the β-barrel. The amino-terminal domain of FimD is observed in an ideal position to catalyse incorporation of a newly recruited chaperone-subunit complex. The FimD-FimC-FimH structure provides unique insights into the pilus subunit incorporation cycle, and captures the first view of a protein transporter in the act of secreting its cognate substrate.
authors.affiliation: Institute of Structural and Molecular Biology, University College London and Birkbeck College, Malet Street, London WC1E 7HX, UK.
authors.forename: Gilles
authors.initials: G
authors.lastname: Phan
authors.forename: Han
authors.initials: H
authors.lastname: Remaut
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: William J
authors.initials: WJ
authors.lastname: Allen
authors.forename: Katharina F
authors.initials: KF
authors.lastname: Pirker
authors.forename: Andrey
authors.initials: A
authors.lastname: Lebedev
authors.forename: Nadine S
authors.initials: NS
authors.lastname: Henderson
authors.forename: Sebastian
authors.initials: S
authors.lastname: Geibel
authors.forename: Ender
authors.initials: E
authors.lastname: Volkan
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.forename: Micha B A
authors.initials: MB
authors.lastname: Kunze
authors.forename: Jerome S
authors.initials: JS
authors.lastname: Pinkner
authors.forename: Bradley
authors.initials: B
authors.lastname: Ford
authors.forename: Christopher W M
authors.initials: CW
authors.lastname: Kay
authors.forename: Huilin
authors.initials: H
authors.lastname: Li
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Hultgren
authors.forename: David G
authors.initials: DG
authors.lastname: Thanassi
authors.forename: Gabriel
authors.initials: G
authors.lastname: Waksman
mesh_terms: D018830:Adhesins, Escherichia coli / Q000737:chemistry* / Q000378:metabolism; D003460:Crystallization; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D036781:Fimbriae Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D020836:Protein Structure, Quaternary
chemical_list: D018830:Adhesins, Escherichia coli; D029968:Escherichia coli Proteins; C489721:fimC protein, E coli; C489283:fimD protein, E coli; C058769:fimH protein, E coli; D036781:Fimbriae Proteins