2b5i

From Proteopedia

Revision as of 22:54, 24 March 2013

Template:STRUCTURE 2b5i

cytokine receptor complex

Template:ABSTRACT PUBMED 16293754

Disease

[IL2RA_HUMAN] Genetic variations in IL2RA are associated with susceptibility to diabetes mellitus insulin-dependent type 10 (IDDM10) [MIM:601942]. A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.^[1] [IL2_HUMAN] Note=A chromosomal aberration involving IL2 is found in a form of T-cell acute lymphoblastic leukemia (T-ALL). Translocation t(4;16)(q26;p13) with involves TNFRSF17. [IL2RG_HUMAN] Defects in IL2RG are the cause of severe combined immunodeficiency X-linked T-cell-negative/B-cell-positive/NK-cell-negative (XSCID) [MIM:300400]; also known as agammaglobulinemia Swiss type. A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.^{[2][3][4][5][6][7][8][9][10][11]} Defects in IL2RG are the cause of X-linked combined immunodeficiency (XCID) [MIM:312863]. XCID is a less severe form of X-linked immunodeficiency with a less severe degree of deficiency in cellular and humoral immunity than that seen in XSCID.^[12][13]

Function

[IL2RA_HUMAN] Receptor for interleukin-2. [IL2_HUMAN] Produced by T-cells in response to antigenic or mitogenic stimulation, this protein is required for T-cell proliferation and other activities crucial to regulation of the immune response. Can stimulate B-cells, monocytes, lymphokine-activated killer cells, natural killer cells, and glioma cells. [IL2RG_HUMAN] Common subunit for the receptors for a variety of interleukins. [IL2RB_HUMAN] Receptor for interleukin-2. This beta subunit is involved in receptor mediated endocytosis and transduces the mitogenic signals of IL2.

About this Structure

2b5i is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

See Also

• Interleukin
• Interleukin receptor

Reference

• Wang X, Rickert M, Garcia KC. Structure of the quaternary complex of interleukin-2 with its alpha, beta, and gammac receptors. Science. 2005 Nov 18;310(5751):1159-63. PMID:16293754 doi:310/5751/1159

1. ↑ Lowe CE, Cooper JD, Brusko T, Walker NM, Smyth DJ, Bailey R, Bourget K, Plagnol V, Field S, Atkinson M, Clayton DG, Wicker LS, Todd JA. Large-scale genetic fine mapping and genotype-phenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes. Nat Genet. 2007 Sep;39(9):1074-82. Epub 2007 Aug 5. PMID:17676041 doi:10.1038/ng2102
2. ↑ Puck JM, Deschenes SM, Porter JC, Dutra AS, Brown CJ, Willard HF, Henthorn PS. The interleukin-2 receptor gamma chain maps to Xq13.1 and is mutated in X-linked severe combined immunodeficiency, SCIDX1. Hum Mol Genet. 1993 Aug;2(8):1099-104. PMID:8401490
3. ↑ DiSanto JP, Dautry-Varsat A, Certain S, Fischer A, de Saint Basile G. Interleukin-2 (IL-2) receptor gamma chain mutations in X-linked severe combined immunodeficiency disease result in the loss of high-affinity IL-2 receptor binding. Eur J Immunol. 1994 Feb;24(2):475-9. PMID:8299698
4. ↑ Markiewicz S, Subtil A, Dautry-Varsat A, Fischer A, de Saint Basile G. Detection of three nonsense mutations and one missense mutation in the interleukin-2 receptor gamma chain gene in SCIDX1 that differently affect the mRNA processing. Genomics. 1994 May 1;21(1):291-3. PMID:8088810 doi:http://dx.doi.org/10.1006/geno.1994.1265
5. ↑ Ishii N, Asao H, Kimura Y, Takeshita T, Nakamura M, Tsuchiya S, Konno T, Maeda M, Uchiyama T, Sugamura K. Impairment of ligand binding and growth signaling of mutant IL-2 receptor gamma-chains in patients with X-linked severe combined immunodeficiency. J Immunol. 1994 Aug 1;153(3):1310-7. PMID:8027558
6. ↑ DiSanto JP, Rieux-Laucat F, Dautry-Varsat A, Fischer A, de Saint Basile G. Defective human interleukin 2 receptor gamma chain in an atypical X chromosome-linked severe combined immunodeficiency with peripheral T cells. Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9466-70. PMID:7937790
7. ↑ Pepper AE, Buckley RH, Small TN, Puck JM. Two mutational hotspots in the interleukin-2 receptor gamma chain gene causing human X-linked severe combined immunodeficiency. Am J Hum Genet. 1995 Sep;57(3):564-71. PMID:7668284
8. ↑ Clark PA, Lester T, Genet S, Jones AM, Hendriks R, Levinsky RJ, Kinnon C. Screening for mutations causing X-linked severe combined immunodeficiency in the IL-2R gamma chain gene by single-strand conformation polymorphism analysis. Hum Genet. 1995 Oct;96(4):427-32. PMID:7557965
9. ↑ Puck JM, Pepper AE, Bedard PM, Laframboise R. Female germ line mosaicism as the origin of a unique IL-2 receptor gamma-chain mutation causing X-linked severe combined immunodeficiency. J Clin Invest. 1995 Feb;95(2):895-9. PMID:7860773 doi:http://dx.doi.org/10.1172/JCI117740
10. ↑ Stephan V, Wahn V, Le Deist F, Dirksen U, Broker B, Muller-Fleckenstein I, Horneff G, Schroten H, Fischer A, de Saint Basile G. Atypical X-linked severe combined immunodeficiency due to possible spontaneous reversion of the genetic defect in T cells. N Engl J Med. 1996 Nov 21;335(21):1563-7. PMID:8900089 doi:10.1056/NEJM199611213352104
11. ↑ Jones AM, Clark PA, Katz F, Genet S, McMahon C, Alterman L, Cant A, Kinnon C. B-cell-negative severe combined immunodeficiency associated with a common gamma chain mutation. Hum Genet. 1997 May;99(5):677-80. PMID:9150740
12. ↑ Schmalstieg FC, Leonard WJ, Noguchi M, Berg M, Rudloff HE, Denney RM, Dave SK, Brooks EG, Goldman AS. Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency. J Clin Invest. 1995 Mar;95(3):1169-73. PMID:7883965 doi:http://dx.doi.org/10.1172/JCI117765
13. ↑ Sharfe N, Shahar M, Roifman CM. An interleukin-2 receptor gamma chain mutation with normal thymus morphology. J Clin Invest. 1997 Dec 15;100(12):3036-43. PMID:9399950 doi:10.1172/JCI119858