6HGU

Crystal Structure of an anti-APP-tag Fab


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.207 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.188 

wwPDB Validation   3D Report Full Report


This is version 2.2 of the entry. See complete history


Literature

Structural Analysis Reveals that the Cytokine IL-17F Forms a Homodimeric Complex with Receptor IL-17RC to Drive IL-17RA-Independent Signaling.

Goepfert, A.Lehmann, S.Blank, J.Kolbinger, F.Rondeau, J.M.

(2020) Immunity 52: 499-512.e5

  • DOI: https://doi.org/10.1016/j.immuni.2020.02.004
  • Primary Citation of Related Structures:  
    6HG4, 6HG9, 6HGA, 6HGO, 6HGU

  • PubMed Abstract: 

    Interleukin-17A (IL-17A), IL-17F, and IL-17A/F heterodimers are key cytokines of the innate and adaptive immune response. Dysregulation of the IL-17 pathway contributes to immune pathology, and it is therefore important to elucidate the molecular mechanisms that govern IL-17 recognition and signaling. The receptor IL-17RC is thought to act in concert with IL-17RA to transduce IL-17A-, IL-17F-, and IL-17A/F-mediated signals. We report the crystal structure of the extracellular domain of human IL-17RC in complex with IL-17F. In contrast to the expected model, we found that IL-17RC formed a symmetrical 2:1 complex with IL-17F, thus competing with IL-17RA for cytokine binding. Using biophysical techniques, we showed that IL-17A and IL-17A/F also form 2:1 complexes with IL-17RC, suggesting the possibility of IL-17RA-independent IL-17 signaling pathways. The crystal structure of the IL-17RC:IL-17F complex provides a structural basis for IL-17F signaling through IL-17RC, with potential therapeutic applications for respiratory allergy and inflammatory bowel diseases.


  • Organizational Affiliation

    Novartis Institutes for BioMedical Research, Novartis Pharma AG, 4002 Basel, Switzerland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
anti-APP-tag Fab heavy-chainA,
C [auth H]
222Mus musculusMutation(s): 0 
Entity Groups  
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Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
anti-APP-tag Fab light-chainB,
D [auth L]
219Mus musculusMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.207 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.188 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 61.24α = 109.76
b = 67.84β = 92.36
c = 77.86γ = 115.3
Software Package:
Software NamePurpose
BUSTERrefinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
PDB_EXTRACTdata extraction

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2019-11-20
    Type: Initial release
  • Version 2.0: 2020-03-11
    Changes: Polymer sequence
  • Version 2.1: 2020-06-03
    Changes: Database references
  • Version 2.2: 2024-01-17
    Changes: Data collection, Database references, Refinement description