caa a22 4500 528792458 20191012075523.0 cr unu---uuuuu 180924s2016 xx s 000 0 eng 2041-1723 10.1038/ncomms10738 doi 10.1038/ncomms10738 doi (EDOC)oai:edoc.unibas.ch:42191 (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/114263 26948702 pmid Catch-bond mechanism of the bacterial adhesin FimH [Elektronische Daten] [Maximilian M. Sauer, Roman P. Jakob, Jonathan Eras, Sefer Baday, Deniz Eris, Giulio Navarra, Simon Bernèche, Beat Ernst, Timm Maier, Rudi Glockshuber] Nat Commun Open access ethresearch 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. Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0 ethresearch Sauer Maximilian M. joint author Jakob Roman P. joint author Eras Jonathan joint author Baday Sefer joint author Eris Deniz joint author Navarra Giulio joint author Bernèche Simon joint author Ernst Beat joint author Maier Timm joint author Glockshuber Rudi joint author Nature communications 7, p. 10738 2041-1723 https://edoc.unibas.ch/42191/1/ncomms10738.pdf text/html WWW-Backlink auf das Repository 1 Article edoc PeerReviewed edoc peerstatus EDOC 856 40 https://edoc.unibas.ch/42191/1/ncomms10738.pdf text/html WWW-Backlink auf das Repository EDOC 700 1- Sauer Maximilian M. joint author EDOC 700 1- Jakob Roman P. joint author EDOC 700 1- Eras Jonathan joint author EDOC 700 1- Baday Sefer joint author EDOC 700 1- Eris Deniz joint author EDOC 700 1- Navarra Giulio joint author EDOC 700 1- Bernèche Simon joint author EDOC 700 1- Ernst Beat joint author EDOC 700 1- Maier Timm joint author EDOC 700 1- Glockshuber Rudi joint author EDOC 773 0- Nature communications 7, p. 10738 2041-1723 ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/114263 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Sauer Maximilian M. joint author ETHRESEARCH 700 1- Jakob Roman P. joint author ETHRESEARCH 700 1- Eras Jonathan joint author ETHRESEARCH 700 1- Baday Sefer joint author ETHRESEARCH 700 1- Eriş Deniz joint author ETHRESEARCH 700 1- Navarra Giulio joint author ETHRESEARCH 700 1- Berneche Simon joint author ETHRESEARCH 700 1- Ernst Beat joint author ETHRESEARCH 700 1- Maier Timm joint author ETHRESEARCH 700 1- Glockshuber Rudi joint author ETHRESEARCH 773 0- Nature Communications London : Nature Publishing Group 7, p. 10738 2041-1723 BK010053 XK010053 XK010000 EDOC EDOC EDOC Article ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access