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.
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This work was funded by Medical Research Council grant 85602 to G.W. D.B. and E.P. are supported by grant P41 GM103533 from the National Institute of General Medical Studies at the US National Institutes of Health (NIH). S.J.H. was supported by grant AI029549 from the National Institute of Allergy and Infectious Disease at the NIH. We thank the staff of beamline ID23-1 at the European Synchrotron Radiation Facility, the staff of beamline IO2 at the Diamond Light source and A. Cole for technical assistance during data collection.
The authors declare no competing financial interests.
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Geibel, S., Procko, E., Hultgren, S. et al. Structural and energetic basis of folded-protein transport by the FimD usher. Nature 496, 243–246 (2013). https://doi.org/10.1038/nature12007
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