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protein Protein-protein interface(s) links
Cytokine/receptor PDB id
1j7v
Jmol
Contents
Protein chains
150 a.a. *
205 a.a. *
Waters ×21
* Residue conservation analysis
PDB id:
1j7v
Name: Cytokine/receptor
Title: Human il-10 / il-10r1 complex
Structure: Interleukin-10. Chain: l. Synonym: il-10. Cytokine synthesis inhibitory factor. Csif. Engineered: yes. Interleukin-10 receptor alpha chain. Chain: r. Fragment: extracellular domain, residues 22-235. Synonym: il-10r1. Il-10r-a. Engineered: yes.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227. Expression_system_cell_line: schneider cells
Biol. unit: Tetramer (from PDB file)
Resolution:
2.90Å     R-factor:   0.231     R-free:   0.286
Authors: K.Josephson,N.Logsdon,M.R.Walter
Key ref:
K.Josephson et al. (2001). Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site. Immunity, 15, 35-46. PubMed id: 11485736 DOI: 10.1016/S1074-7613(01)00169-8
Date:
18-May-01     Release date:   19-Sep-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P22301  (IL10_HUMAN) -  Interleukin-10
Seq:
Struc: 		178 a.a.
150 a.a.
Protein chain
Pfam   ArchSchema ?
Q13651  (I10R1_HUMAN) -  Interleukin-10 receptor subunit alpha
Seq:
Struc: 		 
Seq:
Struc: 		578 a.a.
205 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 6 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   3 terms 
  Biological process     negative regulation of growth of symbiont in host   51 terms 
  Biochemical function     protein binding     4 terms  

 

 
DOI no: 10.1016/S1074-7613(01)00169-8 Immunity 15:35-46 (2001)
PubMed id: 11485736  
 
 
Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site.
K.Josephson, N.J.Logsdon, M.R.Walter.
 
  ABSTRACT  
 
Interleukin 10 (IL-10) is a dimeric cytokine that plays a central role in suppressing inflammatory responses. These activities are dependent on the interaction of IL-10 with its high-affinity receptor (IL-10R1). This intermediate complex must subsequently recruit the low-affinity IL-10R2 chain before cell signaling can occur. Here we report the 2.9 A crystal structure of IL-10 bound to a soluble form of IL-10R1 (sIL-10R1). The complex consists of two IL-10s and four sIL-10R1 molecules. Several residues in the IL-10/sIL-10R1 interface are conserved in all IL-10 homologs and their receptors. The data suggests that formation of the active IL-10 signaling complex occurs by a novel molecular recognition paradigm where IL-10R1 and IL-10R2 both recognize the same binding site on IL-10.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Structure of the IL-10 Receptor Complex(A) Ribbon diagram of the 1:2 IL-10/sIL-10R1 complex viewed perpendicular to the two-fold axis of IL-10.(B) Ribbon diagram of the 2:4 IL-10/sIL-10R1 complex viewed down the two-fold axis of IL-10. The box outlines the location of the site IIa interface shown in Figure 3D 		Figure 3.
Figure 3. Molecular Details of the Site I and Site II Interfaces(A) The site Ia interface. IL-10 residues are cyan and sIL-10R1 residues are gold. Oxygen atoms are red and nitrogen atoms are blue. Hydrogen bonds are shown as dotted lines.(B) The site Ib interface. Residues are colored as described in Figure 3A.(C) Molecular surface of the site II interface. The surface of IL-10 is cyan and sIL-10R1 is yellow. The orientation of the figure is equivalent to Figure 1A. Surfaces on IL-10 and sIL-10R1 that form the site IIa and IIb are shown in red and green, respectively. The adjacent 1:2 complex is shown as a ribbon and colored as described in Figure 1B.(D) Close-up of the site IIa interface. Color coding is as described in Figure 1 and Figure 3. Sites Ia, Ib, and IIa are labeled in parenthesis. The box in Figure 1B shows the location of this Figure with respect to the 2:4 complex
 
  The above figures are reprinted by permission from Cell Press: Immunity (2001, 15, 35-46) copyright 2001.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
19833230 A.L.Hughes, S.Irausquin, and R.Friedman (2010).
The evolutionary biology of poxviruses.
  Infect Genet Evol, 10, 50-59.  
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.  
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.  
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.  
21115385 R.Sabat, G.Grütz, K.Warszawska, S.Kirsch, E.Witte, K.Wolk, and J.Geginat (2010).
Biology of interleukin-10.
  Cytokine Growth Factor Rev, 21, 331-344.  
20462497 S.I.Yoon, B.C.Jones, N.J.Logsdon, B.D.Harris, A.Deshpande, S.Radaeva, B.A.Halloran, B.Gao, and M.R.Walter (2010).
Structure and mechanism of receptor sharing by the IL-10R2 common chain.
  Structure, 18, 638-648.
PDB code: 3lqm
19890111 E.O.Glocker, D.Kotlarz, K.Boztug, E.M.Gertz, A.A.Schäffer, F.Noyan, M.Perro, J.Diestelhorst, A.Allroth, D.Murugan, N.Hätscher, D.Pfeifer, K.W.Sykora, M.Sauer, H.Kreipe, M.Lacher, R.Nustede, C.Woellner, U.Baumann, U.Salzer, S.Koletzko, N.Shah, A.W.Segal, A.Sauerbrey, S.Buderus, S.B.Snapper, B.Grimbacher, and C.Klein (2009).
Inflammatory bowel disease and mutations affecting the interleukin-10 receptor.
  N Engl J Med, 361, 2033-2045.  
19457860 H.H.Gad, C.Dellgren, O.J.Hamming, S.Vends, S.R.Paludan, and R.Hartmann (2009).
Interferon-lambda is functionally an interferon but structurally related to the interleukin-10 family.
  J Biol Chem, 284, 20869-20875.
PDB code: 3hhc
19295315 L.H.Tseng, B.Storer, E.Petersdorf, M.T.Lin, J.W.Chien, B.M.Grogan, M.Malkki, P.J.Chen, L.P.Zhao, P.J.Martin, and J.A.Hansen (2009).
IL10 and IL10 receptor gene variation and outcomes after unrelated and related hematopoietic cell transplantation.
  Transplantation, 87, 704-710.  
19142637 M.Terai, Y.Tamura, V.Alexeev, E.Ohtsuka, D.Berd, M.J.Mastrangelo, and T.Sato (2009).
Human interleukin 10 receptor 1/IgG1-Fc fusion proteins: immunoadhesins for human IL-10 with therapeutic potential.
  Cancer Immunol Immunother, 58, 1307-1317.  
19235539 Z.G.Dobreva, L.D.Miteva, and S.A.Stanilova (2009).
The inhibition of JNK and p38 MAPKs downregulates IL-10 and differentially affects c-Jun gene expression in human monocytes.
  Immunopharmacol Immunotoxicol, 31, 195-201.  
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.  
19016528 S.G.Gruber, M.Gloria Luciani, P.Grundtner, A.Zdanov, and C.Gasche (2008).
Differential signaling of cmvIL-10 through common variants of the IL-10 receptor 1.
  Eur J Immunol, 38, 3365-3375.  
18252254 Z.Li, J.J.Strunk, P.Lamken, J.Piehler, and T.Walz (2008).
The EM structure of a type I interferon-receptor complex reveals a novel mechanism for cytokine signaling.
  J Mol Biol, 377, 715-724.  
16757563 A.J.Frodsham, L.Zhang, U.Dumpis, N.A.Taib, S.Best, A.Durham, B.J.Hennig, S.Hellier, S.Knapp, M.Wright, M.Chiaramonte, J.I.Bell, M.Graves, H.C.Whittle, H.C.Thomas, M.R.Thursz, and A.V.Hill (2006).
Class II cytokine receptor gene cluster is a major locus for hepatitis B persistence.
  Proc Natl Acad Sci U S A, 103, 9148-9153.  
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.  
16464504 P.Gupta, Z.Z.Su, I.V.Lebedeva, D.Sarkar, M.Sauane, L.Emdad, M.A.Bachelor, S.Grant, D.T.Curiel, P.Dent, and P.B.Fisher (2006).
mda-7/IL-24: multifunctional cancer-specific apoptosis-inducing cytokine.
  Pharmacol Ther, 111, 596-628.  
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
15374856 H.Li, and J.Li (2005).
Discovery of stable and significant binding motif pairs from PDB complexes and protein interaction datasets.
  Bioinformatics, 21, 314-324.  
15837194 S.I.Yoon, B.C.Jones, N.J.Logsdon, and M.R.Walter (2005).
Same structure, different function crystal structure of the Epstein-Barr virus IL-10 bound to the soluble IL-10R1 chain.
  Structure, 13, 551-564.
PDB codes: 1y6k 1y6m 1y6n
15985167 S.Pletnev, E.Magracheva, A.Wlodawer, and A.Zdanov (2005).
A model of the ternary complex of interleukin-10 with its soluble receptors.
  BMC Struct Biol, 5, 10.  
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
  14746812 J.A.Langer, E.C.Cutrone, and S.Kotenko (2004).
The Class II cytokine receptor (CRF2) family: overview and patterns of receptor-ligand interactions.
  Cytokine Growth Factor Rev, 15, 33-48.  
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.  
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.  
  12842042 J.H.Chill, S.R.Quadt, R.Levy, G.Schreiber, and J.Anglister (2003).
The human type I interferon receptor: NMR structure reveals the molecular basis of ligand binding.
  Structure, 11, 791-802.
PDB codes: 1n6u 1n6v
14580208 S.Pletnev, E.Magracheva, S.Kozlov, G.Tobin, S.V.Kotenko, A.Wlodawer, and A.Zdanov (2003).
Characterization of the recombinant extracellular domains of human interleukin-20 receptors and their complexes with interleukin-19 and interleukin-20.
  Biochemistry, 42, 12617-12624.  
  11929132 H.Fickenscher, S.Hör, H.Küpers, A.Knappe, S.Wittmann, and H.Sticht (2002).
The interleukin-10 family of cytokines.
  Trends Immunol, 23, 89-96.  
  12121653 K.Josephson, B.C.Jones, L.J.Walter, R.DiGiacomo, S.R.Indelicato, and M.R.Walter (2002).
Noncompetitive antibody neutralization of IL-10 revealed by protein engineering and x-ray crystallography.
  Structure, 10, 981-987.
PDB code: 1lk3
12513909 N.J.Logsdon, B.C.Jones, K.Josephson, J.Cook, and M.R.Walter (2002).
Comparison of interleukin-22 and interleukin-10 soluble receptor complexes.
  J Interferon Cytokine Res, 22, 1099-1112.  
  12486876 S.V.Kotenko (2002).
The family of IL-10-related cytokines and their receptors: related, but to what extent?
  Cytokine Growth Factor Rev, 13, 223-240.  
11905829 W.J.Leonard (2001).
Cytokines and immunodeficiency diseases.
  Nat Rev Immunol, 1, 200-208.  
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.