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Catch-bond mechanism of the bacterial adhesin FimH

Sauer, Maximilian M. and Jakob, Roman P. and Eras, Jonathan and Baday, Sefer and Eris, Deniz and Navarra, Giulio and Bernèche, Simon and Ernst, Beat and Maier, Timm and Glockshuber, Rudi. (2016) Catch-bond mechanism of the bacterial adhesin FimH. Nature communications, 7. p. 10738.

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Official URL: http://edoc.unibas.ch/42191/

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Maier)
05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molekulare Pharmazie (Ernst)
UniBasel Contributors:Maier, Timm and Jakob, Roman Peter and Ernst, Beat and Eris, Deniz and Navarra, Giulio and Bernèche, Simon
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
ISSN:2041-1723
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:17 Nov 2016 14:25
Deposited On:22 Mar 2016 16:02

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