4XO8: Crystal structure of the FimH lectin domain from E.coli K12 in complex with heptyl alpha-D-mannopyrannoside

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.
PDB ID: 4XO8Download
MMDB ID: 135918
PDB Deposition Date: 2015/1/16
Updated in MMDB: 2018/07
Experimental Method:
x-ray diffraction
Resolution: 1.698  Å
Source Organism:
Similar Structures:
Biological Unit for 4XO8: monomeric; determined by author and by software (PISA)
Molecular Components in 4XO8
Label Count Molecule
Protein (1 molecule)
Protein Fimh(Gene symbol: fimH)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB