5JR4

Crystal structure of FimH A27V/V163A from E. coli UTI89 bound to FimG N-terminal extension


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.217 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Evolutionary fine-tuning of conformational ensembles in FimH during host-pathogen interactions.

Kalas, V.Pinkner, J.S.Hannan, T.J.Hibbing, M.E.Dodson, K.W.Holehouse, A.S.Zhang, H.Tolia, N.H.Gross, M.L.Pappu, R.V.Janetka, J.Hultgren, S.J.

(2017) Sci Adv 3: e1601944-e1601944

  • DOI: https://doi.org/10.1126/sciadv.1601944
  • Primary Citation of Related Structures:  
    5JQI, 5JR4

  • PubMed Abstract: 

    Positive selection in the two-domain type 1 pilus adhesin FimH enhances Escherichia coli fitness in urinary tract infection (UTI). We report a comprehensive atomic-level view of FimH in two-state conformational ensembles in solution, composed of one low-affinity tense (T) and multiple high-affinity relaxed (R) conformations. Positively selected residues allosterically modulate the equilibrium between these two conformational states, each of which engages mannose through distinct binding orientations. A FimH variant that only adopts the R state is severely attenuated early in a mouse model of uncomplicated UTI but is proficient at colonizing catheterized bladders in vivo or bladder transitional-like epithelial cells in vitro. Thus, the bladder habitat has barrier(s) to R state-mediated colonization possibly conferred by the terminally differentiated bladder epithelium and/or decoy receptors in urine. Together, our studies reveal the conformational landscape in solution, binding mechanisms, and adhesive strength of an allosteric two-domain adhesin that evolved "moderate" affinity to optimize persistence in the bladder during UTI.


  • Organizational Affiliation

    Center for Women's Infectious Disease Research, Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Type 1 fimbiral adhesin FimH279Escherichia coli UTI89Mutation(s): 2 
Gene Names: fimHUTI89_C5017
UniProt
Find proteins for Q1R2J4 (Escherichia coli (strain UTI89 / UPEC))
Explore Q1R2J4 
Go to UniProtKB:  Q1R2J4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ1R2J4
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
FimG N-terminal extension15Escherichia coli UTI89Mutation(s): 0 
UniProt
Find proteins for Q1R2J5 (Escherichia coli (strain UTI89 / UPEC))
Explore Q1R2J5 
Go to UniProtKB:  Q1R2J5
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ1R2J5
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.217 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 122.32α = 90
b = 33.03β = 120.62
c = 72.45γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
iMOSFLMdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-02-22
    Type: Initial release
  • Version 1.1: 2017-04-19
    Changes: Derived calculations
  • Version 1.2: 2018-04-18
    Changes: Data collection, Database references
  • Version 1.3: 2023-09-27
    Changes: Data collection, Database references, Derived calculations, Refinement description