3LB6

The structure of IL-13 in complex with IL-13Ralpha2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.05 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.222 

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Literature

Molecular basis for shared cytokine recognition revealed in the structure of an unusually high affinity complex between IL-13 and IL-13Ralpha2.

Lupardus, P.J.Birnbaum, M.E.Garcia, K.C.

(2010) Structure 18: 332-342

  • DOI: https://doi.org/10.1016/j.str.2010.01.003
  • Primary Citation of Related Structures:  
    3LB6

  • PubMed Abstract: 

    Interleukin-13 is a cytokine important for development of T helper cell type 2 (Th2) responses and plays a critical role in asthma and allergy. The IL-13 Receptor alpha2 (IL-13Ralpha2) is a receptor for IL-13 lacking canonical Jak/STAT signaling functions. Here we present the crystal structure along with a mutational and biophysical analysis of the IL-13/IL-13Ralpha2 complex. While retaining a similar mode of IL-13 binding to its related signaling receptor, IL-13Ralpha1, IL-13Ralpha2 uses peripheral receptor residues unused in the IL-13/IL-13Ralpha1 complex to generate a larger and more complementary interface for IL-13. This results in a four orders of magnitude increase in affinity, to the femtomolar level, compared to IL-13Ralpha1. Alanine scanning mutagenesis of the IL-13 interface reveals several common "hotspot" residues important for binding to both receptors, but also identifies a prominent IL-13Ralpha2-specific contact. These results provide a framework for development of receptor subtype-selective IL-13 antagonists and indicate a decoy function for IL-13Ralpha2.


  • Organizational Affiliation

    Howard Hughes Medical Institute, Department of Molecular and Cellular Physiology, Department of Structural Biology, and Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Interleukin-13132Homo sapiensMutation(s): 0 
Gene Names: IL13NC30
UniProt & NIH Common Fund Data Resources
Find proteins for P35225 (Homo sapiens)
Explore P35225 
Go to UniProtKB:  P35225
PHAROS:  P35225
GTEx:  ENSG00000169194 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP35225
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Interleukin-13 receptor subunit alpha-2B [auth C]380Homo sapiensMutation(s): 1 
UniProt & NIH Common Fund Data Resources
Find proteins for Q14627 (Homo sapiens)
Explore Q14627 
Go to UniProtKB:  Q14627
PHAROS:  Q14627
GTEx:  ENSG00000123496 
Entity Groups  
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UniProt GroupQ14627
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Interleukin-13C [auth B]132Homo sapiensMutation(s): 0 
Gene Names: IL13NC30
UniProt & NIH Common Fund Data Resources
Find proteins for P35225 (Homo sapiens)
Explore P35225 
Go to UniProtKB:  P35225
PHAROS:  P35225
GTEx:  ENSG00000169194 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP35225
Sequence Annotations
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Interleukin-13 receptor subunit alpha-2380Homo sapiensMutation(s): 1 
UniProt & NIH Common Fund Data Resources
Find proteins for Q14627 (Homo sapiens)
Explore Q14627 
Go to UniProtKB:  Q14627
PHAROS:  Q14627
GTEx:  ENSG00000123496 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ14627
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  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.05 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.222 
  • Space Group: I 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 73.37α = 90
b = 86.57β = 96.77
c = 166.788γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
PHENIXrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-03-16
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Data collection, Derived calculations, Structure summary
  • Version 1.3: 2021-10-13
    Changes: Advisory, Database references, Structure summary