spacer
spacer
Go to PDB code: 
protein Protein-protein interface(s) links
Cytokine PDB id
1m4r
Jmol
Contents
Protein chains
142 a.a. *
Waters ×189
* Residue conservation analysis
PDB id:
1m4r
Name: Cytokine
Title: Crystal structure of recombinant human interleukin-22
Structure: Interleukin-22. Chain: a, b. Synonym: il-22, il-10-related t-cell-derived inducible factor, il-tif. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
2.00Å     R-factor:   0.188     R-free:   0.220
Authors: R.A.P.Nagem,D.Colau,L.Dumoutier,J.-C.Renauld,C.Ogata, I.Polikarpov
Key ref:
R.A.Nagem et al. (2002). Crystal structure of recombinant human interleukin-22. Structure, 10, 1051-1062. PubMed id: 12176383 DOI: 10.1016/S0969-2126(02)00797-9
Date:
03-Jul-02     Release date:   07-Jul-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9GZX6  (IL22_HUMAN) -  Interleukin-22
Seq:
Struc: 		179 a.a.
142 a.a.
Key:    PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 

 

 
DOI no: 10.1016/S0969-2126(02)00797-9 Structure 10:1051-1062 (2002)
PubMed id: 12176383  
 
 
Crystal structure of recombinant human interleukin-22.
R.A.Nagem, D.Colau, L.Dumoutier, J.C.Renauld, C.Ogata, I.Polikarpov.
 
  ABSTRACT  
 
Interleukin-22 (IL-10-related T cell-derived inducible factor/IL-TIF/IL-22) is a novel cytokine belonging to the IL-10 family. Recombinant human IL-22 (hIL-22) was found to activate the signal transducers and activators of transcription factors 1 and 3 as well as acute phase reactants in several hepatoma cell lines, suggesting its involvement in the inflammatory response. The crystallographic structure of recombinant hIL-22 has been solved at 2.0 A resolution using the SIRAS method. Contrary to IL-10, the hIL-22 dimer does not present an interpenetration of the secondary-structure elements belonging to the two distinct polypeptide chains but results from interface interactions between monomers. Structural differences between these two cytokines, revealed by the crystallographic studies, clearly indicate that, while a homodimer of IL-10 is required for signaling, hIL-22 most probably interacts with its receptor as a monomer.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. The Contact Surface of the hIL-22 DimerThe figure is colored according to residue hydrophobicity (A and B) and electrostatic potential (C and D). Interface views of monomer A (A and C) and monomer B (B and D) are shown. In parts (A) and (B), the darker the yellow, the greater the hydrophobicity. In parts (C) and (D), areas of negative, positive, and neutral electrostatic potential are depicted in red, blue, and white, respectively. The figures were prepared with GRASP [32].
 
  The above figure is reprinted by permission from Cell Press: Structure (2002, 10, 1051-1062) copyright 2002.  
  Figure was selected by the author.  

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.  
21514178 M.M.Monte, J.Zou, T.Wang, A.Carrington, and C.J.Secombes (2011).
Cloning, expression analysis and bioactivity studies of rainbow trout (Oncorhynchus mykiss) interleukin-22.
  Cytokine, 55, 62-73.  
21166540 W.Ouyang, S.Rutz, N.K.Crellin, P.A.Valdez, and S.G.Hymowitz (2011).
Regulation and functions of the IL-10 family of cytokines in inflammation and disease.
  Annu Rev Immunol, 29, 71.  
20846897 A.Zdanov (2010).
Structural analysis of cytokines comprising the IL-10 family.
  Cytokine Growth Factor Rev, 21, 325-330.  
20454917 D.B.Trivella, J.R.Ferreira-Júnior, L.Dumoutier, J.C.Renauld, and I.Polikarpov (2010).
Structure and function of interleukin-22 and other members of the interleukin-10 family.
  Cell Mol Life Sci, 67, 2909-2935.  
20870448 E.Witte, K.Witte, K.Warszawska, R.Sabat, and K.Wolk (2010).
Interleukin-22: a cytokine produced by T, NK and NKT cell subsets, with importance in the innate immune defense and tissue protection.
  Cytokine Growth Factor Rev, 21, 365-379.  
20712454 H.H.Gad, O.J.Hamming, and R.Hartmann (2010).
The structure of human interferon lambda and what it has taught us.
  J Interferon Cytokine Res, 30, 565-571.  
20655797 K.Witte, E.Witte, R.Sabat, and K.Wolk (2010).
IL-28A, IL-28B, and IL-29: promising cytokines with type I interferon-like properties.
  Cytokine Growth Factor Rev, 21, 237-251.  
20127093 K.Wolk, E.Witte, K.Witte, K.Warszawska, and R.Sabat (2010).
Biology of interleukin-22.
  Semin Immunopathol, 32, 17-31.  
20947410 R.P.Donnelly, F.Sheikh, H.Dickensheets, R.Savan, H.A.Young, and M.R.Walter (2010).
Interleukin-26: an IL-10-related cytokine produced by Th17 cells.
  Cytokine Growth Factor Rev, 21, 393-401.  
21112807 R.Sabat (2010).
IL-10 family of cytokines.
  Cytokine Growth Factor Rev, 21, 315-324.  
21106435 W.Ouyang (2010).
Distinct roles of IL-22 in human psoriasis and inflammatory bowel disease.
  Cytokine Growth Factor Rev, 21, 435-441.  
19734147 K.L.Fuson, M.Zheng, M.Craxton, A.Pataer, R.Ramesh, S.Chada, and R.B.Sutton (2009).
Structural mapping of post-translational modifications in human interleukin-24: role of N-linked glycosylation and disulfide bonds in secretion and activity.
  J Biol Chem, 284, 30526-30533.  
  19193995 L.Watanabe, P.R.de Moura, A.S.Nascimento, D.Colau, L.Dumoutier, J.C.Renauld, and I.Polikarpov (2009).
Crystallization and preliminary X-ray diffraction analysis of human IL-22 bound to its soluble decoy receptor IL-22BP.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 102-104.  
  18391423 B.C.Jones, N.J.Logsdon, and M.R.Walter (2008).
Crystallization and preliminary X-ray diffraction analysis of human IL-22 bound to the extracellular IL-22R1 chain.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 266-269.  
18599299 B.C.Jones, N.J.Logsdon, and M.R.Walter (2008).
Structure of IL-22 bound to its high-affinity IL-22R1 chain.
  Structure, 16, 1333-1344.
PDB code: 3dgc
18024507 M.de Oliveira Neto, J.R.Ferreira, D.Colau, H.Fischer, A.S.Nascimento, A.F.Craievich, L.Dumoutier, J.C.Renauld, and I.Polikarpov (2008).
Interleukin-22 forms dimers that are recognized by two interleukin-22R1 receptor chains.
  Biophys J, 94, 1754-1765.  
17238830 J.B.Mumm, S.Ekmekcioglu, N.J.Poindexter, S.Chada, and E.A.Grimm (2006).
Soluble human MDA-7/IL-24: characterization of the molecular form(s) inhibiting tumor growth and stimulating monocytes.
  J Interferon Cytokine Res, 26, 877-886.  
17030002 K.Wolk, and R.Sabat (2006).
Interleukin-22: a novel T- and NK-cell derived cytokine that regulates the biology of tissue cells.
  Cytokine Growth Factor Rev, 17, 367-380.  
16784489 L.Hummelshoj, L.P.Ryder, and L.K.Poulsen (2006).
The role of the interleukin-10 subfamily members in immunoglobulin production by human B cells.
  Scand J Immunol, 64, 40-47.  
16982608 S.I.Yoon, N.J.Logsdon, F.Sheikh, R.P.Donnelly, and M.R.Walter (2006).
Conformational changes mediate interleukin-10 receptor 2 (IL-10R2) binding to IL-10 and assembly of the signaling complex.
  J Biol Chem, 281, 35088-35096.
PDB code: 2h24
15922016 C.D.Krause, and S.Pestka (2005).
Evolution of the Class 2 cytokines and receptors, and discovery of new friends and relatives.
  Pharmacol Ther, 106, 299-346.  
15618397 J.Klein, and N.Nikolaidis (2005).
The descent of the antibody-based immune system by gradual evolution.
  Proc Natl Acad Sci U S A, 102, 169-174.  
15983417 T.Xu, N.J.Logsdon, and M.R.Walter (2005).
Structure of insect-cell-derived IL-22.
  Acta Crystallogr D Biol Crystallogr, 61, 942-950.
PDB code: 1ykb
15032600 S.Pestka, C.D.Krause, D.Sarkar, M.R.Walter, Y.Shi, and P.B.Fisher (2004).
Interleukin-10 and related cytokines and receptors.
  Annu Rev Immunol, 22, 929-979.  
15213397 T.Xu, N.J.Logsdon, and M.R.Walter (2004).
Crystallization and X-ray diffraction analysis of insect-cell-derived IL-22.
  Acta Crystallogr D Biol Crystallogr, 60, 1295-1298.  
12667095 B.E.Rich (2003).
IL-20: a new target for the treatment of inflammatory skin disease.
  Expert Opin Ther Targets, 7, 165-174.  
12403790 C.Chang, E.Magracheva, S.Kozlov, S.Fong, G.Tobin, S.Kotenko, A.Wlodawer, and A.Zdanov (2003).
Crystal structure of interleukin-19 defines a new subfamily of helical cytokines.
  J Biol Chem, 278, 3308-3313.
PDB code: 1n1f
12974481 J.C.Renauld (2003).
Class II cytokine receptors and their ligands: key antiviral and inflammatory modulators.
  Nat Rev Immunol, 3, 667-676.  
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.