title: Fiber formation across the bacterial outer membrane by the chaperone/usher pathway.
abstract: Gram-negative pathogens commonly exhibit adhesive pili on their surfaces that mediate specific attachment to the host. A major class of pili is assembled via the chaperone/usher pathway. Here, the structural basis for pilus fiber assembly and secretion performed by the outer membrane assembly platform--the usher--is revealed by the crystal structure of the translocation domain of the P pilus usher PapC and single particle cryo-electron microscopy imaging of the FimD usher bound to a translocating type 1 pilus assembly intermediate. These structures provide molecular snapshots of a twinned-pore translocation machinery in action. Unexpectedly, only one pore is used for secretion, while both usher protomers are used for chaperone-subunit complex recruitment. The translocating pore itself comprises 24 beta strands and is occluded by a folded plug domain, likely gated by a conformationally constrained beta-hairpin. These structures capture the secretion of a virulence factor across the outer membrane of gram-negative bacteria.
authors.affiliation: Institute of Structural Molecular Biology, University College London and Birkbeck College, Malet Street, London, WC1E 7HX, United Kingdom.
authors.forename: Han
authors.initials: H
authors.lastname: Remaut
authors.forename: Chunyan
authors.initials: C
authors.lastname: Tang
authors.forename: Nadine S
authors.initials: NS
authors.lastname: Henderson
authors.forename: Jerome S
authors.initials: JS
authors.lastname: Pinkner
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
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
authors.forename: Huilin
authors.initials: H
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D053898:Biosynthetic Pathways; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000737:chemistry* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D036781:Fimbriae Proteins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D010861:Fimbriae, Bacterial / Q000648:ultrastructure*; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000378:metabolism*; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D018272:Porins / Q000737:chemistry / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; D018832:Molecular Chaperones; D046912:Multiprotein Complexes; D018272:Porins; C111243:atpG protein, E coli; C489721:fimC protein, E coli; C489283:fimD protein, E coli; D036781:Fimbriae Proteins