PDBsum entry 4xod

Cell adhesion

PDB id: 4xod

Contents

Protein chains

13 a.a.

279 a.a.

Waters ×597

PDB id:

4xod

Name:

Cell adhesion

Title:

Crystal structure of a fimh Dsg complex from e.Coli f18

Structure:

Fimg protein. Chain: b. Fragment: unp residues 24-37. Engineered: yes. Fimh protein. Chain: a. Fragment: unp residues 25-303. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Gene: ecp_4654. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: ecp_4655.

Resolution:

1.14Å R-factor: 0.143 R-free: 0.159

Authors:

R.P.Jakob,M.M.Sauer,R.Glockshuber,T.Maier

Key ref:

M.M.Sauer et al. (2016). Catch-bond mechanism of the bacterial adhesin FimH. Nat Commun, 7, 10738. PubMed id: 26948702 DOI: 10.1038/ncomms10738

Date:

16-Jan-15 Release date: 27-Jan-16

Protein chain

P08190  (FIMG_ECOLI) -  Protein FimG from Escherichia coli (strain K12)

Seq: 167 a.a.

Struc: 13 a.a.

Protein chain

P08191  (FIMH_ECOLI) -  Type 1 fimbrin D-mannose specific adhesin from Escherichia coli (strain K12)

Seq: 300 a.a.

Struc: 279 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1038/ncomms10738

Nat Commun 7:10738 (2016)

PubMed id: 26948702

Catch-bond mechanism of the bacterial adhesin FimH.

M.M.Sauer, R.P.Jakob, J.Eras, S.Baday, D.Eriş, G.Navarra, S.Bernèche, B.Ernst, T.Maier, R.Glockshuber.

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.