Catch-bond mechanism of the bacterial adhesin FimH.
- Sauer MM Institute of Molecular Biology and Biophysics, Department of Biology, ETH, Zurich, Otto-Stern-Weg 5, 8093 Zurich, Switzerland.
- Jakob RP Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
- Eras J Institute of Molecular Biology and Biophysics, Department of Biology, ETH, Zurich, Otto-Stern-Weg 5, 8093 Zurich, Switzerland.
- Baday S Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
- Eriş D Institute of Molecular Pharmacy, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
- Navarra G Institute of Molecular Pharmacy, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
- Bernèche S Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
- Ernst B Institute of Molecular Pharmacy, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
- Maier T Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
- Glockshuber R Institute of Molecular Biology and Biophysics, Department of Biology, ETH, Zurich, Otto-Stern-Weg 5, 8093 Zurich, Switzerland.
- 2016-03-08
Published in:
- Nature communications. - 2016
Adhesins, Escherichia coli
Bacterial Adhesion
Biomechanical Phenomena
Escherichia coli
Escherichia coli Infections
Fimbriae Proteins
Fimbriae, Bacterial
Humans
Ligands
Mannose
Molecular Dynamics Simulation
Protein Binding
Protein Structure, Tertiary
English
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.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1038/ncomms10738
- PMID 26948702
- Persistent URL
- https://sonar.ch/global/documents/153544
Statistics
Document views: 43
File downloads:
- Full-text: 0