Catch-bond mechanism of the bacterial adhesin FimH

Maximilian M. Sauer, Roman P. Jakob, Jonathan Eras, Sefer Baday, Deniz Eriş, Giulio Navarra, Simon Bernèche, Beat Ernst, Timm Maier*, Rudi Glockshuber

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

157 Citations (Scopus)

Abstract

Ligand-receptor interactions that are reinforced by mechanical stress, so-called catch-bonds, play a major role in cell-cell adhesion. They critically contribute to widespread urinary tract infections by pathogenic Escherichia coli strains. These pathogens attach to host epithelia via the adhesin FimH, a two-domain protein at the tip of type I pili recognizing terminal mannoses on epithelial glycoproteins. Here we establish peptide-complemented FimH as a model system for fimbrial FimH function. We reveal a three-state mechanism of FimH catch-bond formation based on crystal structures of all states, kinetic analysis of ligand interaction and molecular dynamics simulations. In the absence of tensile force, the FimH pilin domain allosterically accelerates spontaneous ligand dissociation from the FimH lectin domain by 100,000-fold, resulting in weak affinity. Separation of the FimH domains under stress abolishes allosteric interplay and increases the affinity of the lectin domain. Cell tracking demonstrates that rapid ligand dissociation from FimH supports motility of piliated E. coli on mannosylated surfaces in the absence of shear force.

Original languageEnglish
Article number10738
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 7 Mar 2016
Externally publishedYes

Funding

We thank the staff at the Swiss Light Source (Villigen, Switzerland) for outstanding support for crystallographic data collection and the Imaging Facility as well as Research IT/A, and Mazur at Biozentrum, Basel, for supporting cell-tracking experiments. Discussions with Dr Jochen Reinstein (Max-Planck-Institute for Medical Research) are gratefully acknowledged. This work was supported by the Swiss National Science Foundation (Projects R’Equip 145023 (T.M) and Project 144183 (B.E., T.M. and R.G.), 310030B_138657 (R.G.) and 31003A_156304 (R.G.)). Calculations were performed at sciCORE (http://scicore.unibas.ch/) scientific computing core facility at University of Basel and the Swiss National Supercomputing Centre.

FundersFunder number
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung310030B_138657, 144183, 31003A_156304, R’Equip 145023

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