6GTV

Crystal structure of a FimH*DsG complex from E.coli F18 with bound trimannose


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.189 

wwPDB Validation   3D Report Full Report


This is version 2.1 of the entry. See complete history


Literature

Binding of the Bacterial Adhesin FimH to Its Natural, Multivalent High-Mannose Type Glycan Targets.

Sauer, M.M.Jakob, R.P.Luber, T.Canonica, F.Navarra, G.Ernst, B.Unverzagt, C.Maier, T.Glockshuber, R.

(2019) J Am Chem Soc 141: 936-944

  • DOI: https://doi.org/10.1021/jacs.8b10736
  • Primary Citation of Related Structures:  
    6GTV, 6GTW, 6GTX, 6GTY, 6GTZ, 6GU0

  • PubMed 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 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.


  • Organizational Affiliation

    Institute of Molecular Biology & Biophysics , ETH Zurich , Otto-Stern-Weg 5 , CH-8093 Zurich , Switzerland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
FimH protein
A, C
279Escherichia coli F18+Mutation(s): 0 
Gene Names: ECP_4655fimh
UniProt
Find proteins for A0A0R4I961 (Escherichia coli F18+)
Explore A0A0R4I961 
Go to UniProtKB:  A0A0R4I961
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A0R4I961
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
FimG protein
B, D
14Escherichia coli 536Mutation(s): 0 
UniProt
Find proteins for A0A140UH97 (Escherichia coli O6:K15:H31 (strain 536 / UPEC))
Explore A0A140UH97 
Go to UniProtKB:  A0A140UH97
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A140UH97
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

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Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose
E
3N/A
Glycosylation Resources
GlyTouCan:  G00619DD
GlyCosmos:  G00619DD
GlyGen:  G00619DD
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.189 
  • Space Group: C 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 116.69α = 90
b = 119.21β = 90
c = 120.09γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2019-01-16
    Type: Initial release
  • Version 1.1: 2019-05-01
    Changes: Data collection, Database references
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2024-01-17
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary