Interleukin-10

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Figure 1. IL-10 N-Terminus of helix A
Figure 1. IL-10 N-Terminus of helix A

2H24 is the PDB id assigned to Interleukin-10 (IL-10) after the determination of the crystal structure. IL-10 is a ternary complex that requires specific assembly for proper function. The IL-10 complex is composed of IL-10,IL-10R1,IL-10R2 (R=receptor). The initial step is the formation of IL-10 and IL-10R1, a binary complex that generates a conformational change. This conformational change is required for IL-10R2 to be able to associate with the binary complex and form the ternary complex [1].

The affinity of IL-10R1 and Il-10R2 are not considered to be dependent on the amino acid sequence but something more complex. There are several homolog IL-10s and mimic IL-10s that are able to bind and signal through the IL-10 receptor complex causing overlaying signals with cIL-10 [1]. The completed ternary complex activates the JAK/STAT signaling pathway.
Figure 2. Sequential assembly of the ternary complex
Figure 2. Sequential assembly of the ternary complex
The completion of the ternary complex is dependent on the conformational changes that occur in the N terminus of the helix labelled A. The conformational changes occur when the cIL-10 binds with IL-10R1. There is a positional change of about 1 angstrom at residues between Cys-12 and Leu-46. There are structural features that allow for the large conformational changes, the structural features are a Cys-12 to Cys-108 disulfide bond at the N terminus and Leu-Leu-Leu motifat the C terminus of the AB loop[1].



Contents

IL-10

Interleukin-10 is in the class cytokine.[1] Interleukin-10 is a very powerful anti-inflammatory cytokine that is most commonly found to be produce by moncytes [2]. IL-10 has the ability to be a immunosupressive as well as a anti-angiogenic this means that it has the ability both promot and inhibit tumors[3]. There are many types of cytokines that have many funtions such as antiinflammatory cytokines,cytokine synthesis inhibitory factor and proinflammitory cytokines[4].

There are many interleukins that fall within the cytokine class such as IL-1,IL-2,IL-3,IL-4...IL-31,IL-32,IL-33,IL-3 and IL-35.

2h24, resolution 2.00Å ()
Related: 1inr
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml


Interleukin-10 and Rheumatoid Arthritis

Figure 3. Synovial Joint
Figure 3. Synovial Joint
[5]

IL-10 has been investigated for its role in patients with Rheumatoid Arthritis (RA) as well as those with Osteoarthritis (OA)[4]. RA is an autoimmune disorder that affects the synovial tissues via chronic synovitis. Chronic synovitis often results in joint destruction due to re-absorption of bone and the distruction of cartilage[6] [4]. IL-10 is found to be spontaneously produce in synovial tissue of patients with RA and OA but not in normal synovial tissue. The variation in secretion of IL-10 is thought to be 75% under the control of the genetics of the individual[6]. When IL-10 is present there is an inhibition of the proinflammatory cytokines, namely TFN-α, IL-1α, IL-1β, IL-6, IL-8 [7].


3D structures of interleukin

Interleukin


References

  1. 1.0 1.1 1.2 1.3 Yoon SI, Logsdon NJ, Sheikh F, Donnelly RP, Walter MR. Conformational changes mediate interleukin-10 receptor 2 (IL-10R2) binding to IL-10 and assembly of the signaling complex. J Biol Chem. 2006 Nov 17;281(46):35088-96. Epub 2006 Sep 18. PMID:16982608 doi:10.1074/jbc.M606791200
  2. Hudson LL, Rocca KM, Kuwana M, Pandey JP. Interleukin-10 genotypes are associated with systemic sclerosis and influence disease-associated autoimmune responses. Genes Immun. 2005 May;6(3):274-8. PMID:15772682
  3. Shih CM, Lee YL, Chiou HL, Hsu WF, Chen WE, Chou MC, Lin LY. The involvement of genetic polymorphism of IL-10 promoter in non-small cell lung cancer. Lung Cancer. 2005 Dec;50(3):291-7. Epub 2005 Aug 24. PMID:16122836 doi:10.1016/j.lungcan.2005.07.007
  4. 4.0 4.1 4.2 Katsikis PD, Chu CQ, Brennan FM, Maini RN, Feldmann M. Immunoregulatory role of interleukin 10 in rheumatoid arthritis. J Exp Med. 1994 May 1;179(5):1517-27. PMID:8163935
  5. http://en.wikipedia.org/wiki/Synovial_membrane
  6. 6.0 6.1 Nemec P, Goldbergova MP, Gatterova J, Vasku A, Soucek M. Association of polymorphisms in interleukin-10 gene promoter with autoantibody production in patients with rheumatoid arthritis. Ann N Y Acad Sci. 2009 Sep;1173:501-8. PMID:19758192 doi:10.1111/j.1749-6632.2009.04625.x
  7. de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991 Nov 1;174(5):1209-20. PMID:1940799

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