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- PDB-6gu0: Crystal structure of a FimH*DsG complex from E.coli F18 with boun... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6gu0 | |||||||||
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Title | Crystal structure of a FimH*DsG complex from E.coli F18 with bound dimannoside Man(alpha1-3)Man in space group P213 | |||||||||
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![]() | CELL ADHESION / TYPE I PILUS / CATCH-BOND / LECTIN / UPEC / INFECTION / MANNOSE | |||||||||
Function / homology | ![]() cell adhesion involved in single-species biofilm formation / pilus / metal ion binding Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Jakob, R.P. / Sauer, M.M. / Luber, T. / Canonica, F. / Navarra, G. / Ernst, B. / Unverzagt, C. / Maier, T. / Glockshuber, R. | |||||||||
![]() | ![]() Title: Binding of the Bacterial Adhesin FimH to Its Natural, Multivalent High-Mannose Type Glycan Targets. Authors: Maximilian M Sauer / Roman P Jakob / Thomas Luber / Fabia Canonica / Giulio Navarra / Beat Ernst / Carlo Unverzagt / Timm Maier / Rudi Glockshuber / ![]() ![]() Abstract: Multivalent carbohydrate-lectin interactions at host-pathogen interfaces play a crucial role in the establishment of infections. Although competitive antagonists that prevent pathogen adhesion are ...Multivalent carbohydrate-lectin interactions at host-pathogen interfaces play a crucial role in the establishment of infections. Although competitive antagonists that prevent pathogen adhesion are promising antimicrobial drugs, the molecular mechanisms underlying these complex adhesion processes are still poorly understood. Here, we characterize the interactions between the fimbrial adhesin FimH from uropathogenic Escherichia coli strains and its natural high-mannose type N-glycan binding epitopes on uroepithelial glycoproteins. Crystal structures and a detailed kinetic characterization of ligand-binding and dissociation revealed that the binding pocket of FimH evolved such that it recognizes the terminal α(1-2)-, α(1-3)-, and α(1-6)-linked mannosides of natural high-mannose type N-glycans with similar affinity. We demonstrate that the 2000-fold higher affinity of the domain-separated state of FimH compared to its domain-associated state is ligand-independent and consistent with a thermodynamic cycle in which ligand-binding shifts the association equilibrium between the FimH lectin and the FimH pilin domain. Moreover, we show that a single N-glycan can bind up to three molecules of FimH, albeit with negative cooperativity, so that a molar excess of accessible N-glycans over FimH on the cell surface favors monovalent FimH binding. Our data provide pivotal insights into the adhesion properties of uropathogenic Escherichia coli strains to their target receptors and a solid basis for the development of effective FimH antagonists. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 176.9 KB | Display | ![]() |
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PDB format | ![]() | 141.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 815.8 KB | Display | ![]() |
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Full document | ![]() | 815.7 KB | Display | |
Data in XML | ![]() | 14.7 KB | Display | |
Data in CIF | ![]() | 21.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6gtvC ![]() 6gtwC ![]() 6gtxC ![]() 6gtyC ![]() 6gtzC ![]() 4xoeS S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 29053.260 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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#2: Protein/peptide | Mass: 1416.661 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() ![]() |
#3: Polysaccharide | alpha-D-mannopyranose-(1-3)-methyl alpha-D-mannopyranoside Source method: isolated from a genetically manipulated source |
#4: Chemical | ChemComp-SO4 / |
#5: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop Details: 0.1 M (NH4)2SO4, 0.1 M sodium cacodylate pH 6.5, 30% MPD |
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-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: May 7, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.99999 Å / Relative weight: 1 |
Reflection | Resolution: 2.5→90.96 Å / Num. obs: 24813 / % possible obs: 99.9 % / Redundancy: 20 % / CC1/2: 0.998 / Rrim(I) all: 0.197 / Net I/σ(I): 17.9 |
Reflection shell | Resolution: 2.5→2.65 Å / Redundancy: 20.3 % / Mean I/σ(I) obs: 1.5 / Num. unique obs: 3918 / CC1/2: 0.684 / Rrim(I) all: 2.49 / % possible all: 99.9 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 4XOE Resolution: 2.501→64.315 Å / SU ML: 0.27 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 22.88 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.501→64.315 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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