Structural and energetic basis of folded-protein transport by the FimD usher

DOI: 10.1038/nature12007
PMID: 23579681

Authors: Sebastian Geibel (Birkbeck University of London) , Erik Procko (University of Washington) , Scott Hultgren (Washington University School of Medicine) , David Baker (University of Washington) , Gabriel Waksman (University College London and Birkbeck College)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature , VOL 496 (7444) , PAGES 243 - 246

State: Published (Approved)
Published: April 2013

Abstract: Type?1 pili, produced by uropathogenic Escherichia coli, are multisubunit fibres crucial in recognition of and adhesion to host tissues1. During pilus biogenesis, subunits are recruited to an outer membrane assembly platform, the FimD usher, which catalyses their polymerization and mediates pilus secretion2. The recent determination of the crystal structure of an initiation complex provided insight into the initiation step of pilus biogenesis resulting in pore activation, but very little is known about the elongation steps that follow3. Here, to address this question, we determine the structure of an elongation complex in which the tip complex assembly composed of FimC, FimF, FimG and FimH passes through FimD. This structure demonstrates the conformational changes required to prevent backsliding of the nascent pilus through the FimD pore and also reveals unexpected properties of the usher pore. We show that the circular binding interface between the pore lumen and the folded substrate participates in transport by defining a low-energy pathway along which the nascent pilus polymer is guided during secretion

Journal Keywords: X-Ray; Escherichia; Fimbriae; Fimbriae; Bacterial; Models; Molecular; Protein; Thermodynamics

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography

Added On: 15/04/2013 13:03

Discipline Tags:

Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)