title: Evidence for a novel domain of bacterial outer membrane ushers.
abstract: Many pathogenic bacteria possess adhesive surface organelles (called pili), anchored to their outer membrane, which mediate the first step of infection by binding to host tissue. Pilus biogenesis occurs via the "chaperone-usher" pathway: the usher, a large outer membrane protein, binds complexes of a periplasmic chaperone with pilus subunits, unloads the subunits from the chaperone, and assembles them into the pilus, which is extruded into the extracellular space. Ushers comprise an N-terminal periplasmic domain, a large transmembrane beta-barrel central domain, and a C-terminal periplasmic domain. Since structural data are available only for the N-terminal domain, we performed an in-depth bioinformatic analysis of bacterial ushers. Our analysis led us to the conclusion that the transmembrane beta-barrel region of ushers contains a so far unrecognized soluble domain, the "middle domain", which possesses a beta-sandwich fold. Two other bacterial beta-sandwich domains, the TT0351 protein from Thermus thermophilus and the carbohydrate binding module CBM36 from Paenibacillus polymyxa, are possible distant relatives of the usher "middle domain". Several mutations reported to abolish in vivo pilus formation cluster in this region, underlining its functional importance.
authors.affiliation: Biochemisches Institut der Universität Zürich, Zürich CH-8057, Switzerland. capitani@bioc.unizh.ch
authors.forename: Guido
authors.initials: G
authors.lastname: Capitani
authors.forename: Oliv
authors.initials: O
authors.lastname: Eidam
authors.forename: Markus G
authors.initials: MG
authors.lastname: Grütter
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry*; D029968:Escherichia coli Proteins / Q000737:chemistry*; D036781:Fimbriae Proteins / Q000737:chemistry*; D010861:Fimbriae, Bacterial / Q000737:chemistry; D018832:Molecular Chaperones / Q000737:chemistry*; D008969:Molecular Sequence Data; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D012995:Solubility
chemical_list: D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D018832:Molecular Chaperones; C489283:fimD protein, E coli; D036781:Fimbriae Proteins