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PDBsum entry 1ga3

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protein links
Cytokine PDB id
1ga3
Jmol
Contents
Protein chain
113 a.a. *
* Residue conservation analysis
PDB id:
1ga3
Name: Cytokine
Title: Nmr structure of interleukin-13
Structure: Interleukin-13. Chain: a. Fragment: interleukin-13 (residues 21-132). Synonym: il-13. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: il13. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
NMR struc: 20 models
Authors: E.Z.Eisenmesser,D.A.Horita,A.S.Altieri,R.A.Byrd
Key ref:
E.Z.Eisenmesser et al. (2001). Solution structure of interleukin-13 and insights into receptor engagement. J Mol Biol, 310, 231-241. PubMed id: 11419949 DOI: 10.1006/jmbi.2001.4765
Date:
29-Nov-00     Release date:   04-Jul-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P35225  (IL13_HUMAN) -  Interleukin-13
Seq:
Struc:
146 a.a.
113 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   4 terms 
  Biological process     cellular response to mechanical stimulus   25 terms 
  Biochemical function     protein binding     4 terms  

 

 
DOI no: 10.1006/jmbi.2001.4765 J Mol Biol 310:231-241 (2001)
PubMed id: 11419949  
 
 
Solution structure of interleukin-13 and insights into receptor engagement.
E.Z.Eisenmesser, D.A.Horita, A.S.Altieri, R.A.Byrd.
 
  ABSTRACT  
 
The complex and interrelated function of the interleukin cytokines relies on a range of pro-inflammatory and anti-inflammatory immune responses mediated by an array of receptors, and there is considerable cross-reactivity for related cytokines. Recent findings continue to elucidate the expression patterns of interleukin receptors associated with a range of diseases, including cancer. We report here the first experimentally determined high-resolution structure of human interleukin-13 (IL-13). The experimental structure is significantly different from an earlier homology model, which could have led to improper estimation of receptor interaction surfaces and design of mutational experiments. Similarities between the presented IL-13 structure and the homologous interleukin-4 (IL-4) are discussed. Additionally, mutation data for IL-4 and IL-13 are analyzed and combined with a detailed structural analysis of the IL-4/IL4Ralpha interface that leads us to postulate interactions at the IL-13/receptor interface. The structural comparison is used to interpret the different affinities for various receptors and establishes the basis for further mutational experiments and antagonist design.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Solution structure of human IL-13 and comparison to human IL-4. Helix A is in red, helix B is in magenta, helix C is in orange and helix D is in green. (a) Stereo superposition of 20 of the lowest-energy structures of IL-13. (b) Ribbon trace of the lowest-energy structure of IL-13. (c) Ribbon trace of the X-ray crystal structure of IL-4[21]. All Figures were created with MOLMOL [53].
Figure 6.
Figure 6. Comparison of the surfaces formed by helices A and D of human IL-13, human IL-4, and human IL-2 that affect specificity to either the IL4Ra or gc receptor. (a) IL-13, (b) IL-4, and (c) IL-2. Acidic residue are colored red, basic residues are colored blue, and uncharged residues are colored gray.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2001, 310, 231-241) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
18560827 M.Ohtani, N.Hayashi, K.Hashimoto, T.Nakanishi, and J.M.Dijkstra (2008).
Comprehensive clarification of two paralogous interleukin 4/13 loci in teleost fish.
  Immunogenetics, 60, 383-397.  
17565991 K.Bondensgaard, J.Breinholt, D.Madsen, D.H.Omkvist, L.Kang, A.Worsaae, P.Becker, C.B.Schiødt, and S.A.Hjorth (2007).
The existence of multiple conformers of interleukin-21 directs engineering of a superpotent analogue.
  J Biol Chem, 282, 23326-23336.
PDB code: 2oqp
17094811 E.S.Wong, L.J.Young, A.T.Papenfuss, and K.Belov (2006).
In silico identification of opossum cytokine genes suggests the complexity of the marsupial immune system rivals that of eutherian mammals.
  Immunome Res, 2, 4.  
16640778 M.Kraich, M.Klein, E.Patiño, H.Harrer, J.Nickel, W.Sebald, and T.D.Mueller (2006).
A modular interface of IL-4 allows for scalable affinity without affecting specificity for the IL-4 receptor.
  BMC Biol, 4, 13.
PDB codes: 2b8u 2b8x 2b8y 2b8z 2b90 2b91 2d48
16374783 Y.J.Huang, R.Tejero, R.Powers, and G.T.Montelione (2006).
A topology-constrained distance network algorithm for protein structure determination from NOESY data.
  Proteins, 62, 587-603.  
  15711639 F.D.Vladich, S.M.Brazille, D.Stern, M.L.Peck, R.Ghittoni, and D.Vercelli (2005).
IL-13 R130Q, a common variant associated with allergy and asthma, enhances effector mechanisms essential for human allergic inflammation.
  J Clin Invest, 115, 747-754.  
15870068 K.Arima, K.Sato, G.Tanaka, S.Kanaji, T.Terada, E.Honjo, R.Kuroki, Y.Matsuo, and K.Izuhara (2005).
Characterization of the interaction between interleukin-13 and interleukin-13 receptors.
  J Biol Chem, 280, 24915-24922.  
  15068667 A.B.Madhankumar, A.Mintz, and W.Debinski (2004).
Interleukin 13 mutants of enhanced avidity toward the glioma-associated receptor, IL13Ralpha2.
  Neoplasia, 6, 15-22.  
12189139 A.B.Madhankumar, A.Mintz, and W.Debinski (2002).
Alanine-scanning mutagenesis of alpha-helix D segment of interleukin-13 reveals new functionally important residues of the cytokine.
  J Biol Chem, 277, 43194-43205.  
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 code is shown on the right.