spacer
spacer

PDBsum entry 3lb6

Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Signaling protein/signaling protein PDB id
3lb6
Jmol
Contents
Protein chains
109 a.a. *
252 a.a. *
286 a.a. *
Ligands
NAG ×2
Metals
_CA ×2
Waters ×31
* Residue conservation analysis
PDB id:
3lb6
Name: Signaling protein/signaling protein
Title: The structure of il-13 in complex with il-13ralpha2
Structure: Interleukin-13. Chain: a. Synonym: il-13. Engineered: yes. Interleukin-13 receptor subunit alpha-2. Chain: c. Engineered: yes. Mutation: yes. Interleukin-13.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: il13, nc30. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.
Resolution:
3.05Å     R-factor:   0.222     R-free:   0.269
Authors: P.J.Lupardus,K.C.Garcia,M.E.Birnbaum
Key ref: P.J.Lupardus et al. (2010). Molecular basis for shared cytokine recognition revealed in the structure of an unusually high affinity complex between IL-13 and IL-13Ralpha2. Structure, 18, 332-342. PubMed id: 20223216
Date:
07-Jan-10     Release date:   16-Mar-10    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P35225  (IL13_HUMAN) -  Interleukin-13
Seq:
Struc:
146 a.a.
109 a.a.
Protein chain
Pfam   ArchSchema ?
Q14627  (I13R2_HUMAN) -  Interleukin-13 receptor subunit alpha-2
Seq:
Struc:
380 a.a.
252 a.a.*
Protein chain
Pfam   ArchSchema ?
Q14627  (I13R2_HUMAN) -  Interleukin-13 receptor subunit alpha-2
Seq:
Struc:
380 a.a.
286 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     immune response   1 term 
  Biochemical function     cytokine receptor binding     2 terms  

 

 
Structure 18:332-342 (2010)
PubMed id: 20223216  
 
 
Molecular basis for shared cytokine recognition revealed in the structure of an unusually high affinity complex between IL-13 and IL-13Ralpha2.
P.J.Lupardus, M.E.Birnbaum, K.C.Garcia.
 
  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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
22902366 J.Elegheert, N.Bracke, P.Pouliot, I.Gutsche, A.V.Shkumatov, N.Tarbouriech, K.Verstraete, A.Bekaert, W.P.Burmeister, D.I.Svergun, B.N.Lambrecht, B.Vergauwen, and S.N.Savvides (2012).
Allosteric competitive inactivation of hematopoietic CSF-1 signaling by the viral decoy receptor BARF1.
  Nat Struct Mol Biol, 19, 938-947.
PDB codes: 3uez 3uf2 3uf5 4adf 4adq
21377040 M.Akdis, S.Burgler, R.Crameri, T.Eiwegger, H.Fujita, E.Gomez, S.Klunker, N.Meyer, L.O'Mahony, O.Palomares, C.Rhyner, N.Quaked, A.Schaffartzik, W.Van De Veen, S.Zeller, M.Zimmermann, and C.A.Akdis (2011).
Interleukins, from 1 to 37, and interferon-γ: receptors, functions, and roles in diseases.
  J Allergy Clin Immunol, 127, 701.  
20821041 S.Agrawal, and S.Gupta (2011).
TLR1/2, TLR7, and TLR9 signals directly activate human peripheral blood naive and memory B cell subsets to produce cytokines, chemokines, and hematopoietic growth factors.
  J Clin Immunol, 31, 89-98.  
21064130 S.K.Madala, M.A.Dolan, D.Sharma, T.R.Ramalingam, M.S.Wilson, M.M.Mentink-Kane, D.C.Masison, and T.A.Wynn (2011).
Mapping mouse IL-13 binding regions using structure modeling, molecular docking, and high-density peptide microarray analysis.
  Proteins, 79, 282-293.  
20223207 A.A.Kossiakoff, and S.Rizk (2010).
Keeping signaling in check.
  Structure, 18, 275-276.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.