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

TitleStructural and energetic basis of folded-protein transport by the FimD usher
Publication TypeJournal Article
Year of Publication2013
AuthorsGeibel, S., Procko E., Hultgren S. J., Baker D., & Waksman G.
Date Published2013 Apr 11
KeywordsCollaborative Publication, Crystallography, X-Ray, Escherichia coli, Escherichia coli Proteins, Fimbriae Proteins, Fimbriae, Bacterial, Models, Molecular, Protein Conformation, Protein Folding, Protein Stability, Protein Transport, Thermodynamics

Type 1 pili, produced by uropathogenic Escherichia coli, are multisubunit fibres crucial in recognition of and adhesion to host tissues. During pilus biogenesis, subunits are recruited to an outer membrane assembly platform, the FimD usher, which catalyses their polymerization and mediates pilus secretion. 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 follow. 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.


Alternate JournalNature
Geibel_nature12007_13S.pdf1.18 MB