From Proteopedia

proteopedia linkproteopedia link

Revision as of 13:40, 13 October 2010 (edit) David Canner (Talk | contribs) m (Sandbox 165 moved to Interleukin-10) ← Previous diff		Revision as of 13:41, 13 October 2010 (edit) (undo) David Canner (Talk | contribs) Next diff →
Line 1:		Line 1:
-	== '''Interleukin-10''' ==
	[[Image:2h24.png|right|thumb| Figure 1. IL-10 N-Terminus of helix A ]]		[[Image:2h24.png|right|thumb| 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 <ref name="ref1">PMID:16982608</ref>.		'''[[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 <ref name="ref1">PMID:16982608</ref>.

---

Revision as of 13:41, 13 October 2010

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. 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].

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.

spinqualitylabelsall models PDB ID 2h24 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
2h24, resolution 2.00Å ()
Related:	1inr
Structural annotation: Resources: InterPro : Ipr000098, Ipr009079, Ipr012352, Ipr012351 Pfam : PF00726 UniProt : Q71UZ1
Functional annotation: Cellular component: extracellular region Biological process: immune response Molecular function: cytokine activity
Evolutionary conservation: Toggle Conservation Colors: Rows = identical sequences: Further Information: Caveats, Explanation, Complete Results at ConSurfDB
Resources:	FirstGlance, OCA, PDBsum, RCSB
Coordinates:	save as pdb, mmCIF, xml

Interleukin-10 and Rheumatoid Arthritis

^[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].

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

Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. Andrea Gorrell.