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| | <StructureSection load='2erj' size='340' side='right'caption='[[2erj]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='2erj' size='340' side='right'caption='[[2erj]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2erj]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ERJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ERJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2erj]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ERJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ERJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL2RA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IL2RB ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IL2RG ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IL2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2erj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2erj OCA], [https://pdbe.org/2erj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2erj RCSB], [https://www.ebi.ac.uk/pdbsum/2erj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2erj ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2erj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2erj OCA], [https://pdbe.org/2erj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2erj RCSB], [https://www.ebi.ac.uk/pdbsum/2erj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2erj ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/IL2_HUMAN 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. [[https://www.uniprot.org/uniprot/IL2RA_HUMAN IL2RA_HUMAN]] Genetic variations in IL2RA are associated with susceptibility to diabetes mellitus insulin-dependent type 10 (IDDM10) [MIM:[https://omim.org/entry/601942 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.<ref>PMID:17676041</ref> [[https://www.uniprot.org/uniprot/IL2RG_HUMAN 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:[https://omim.org/entry/300400 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.<ref>PMID:8401490</ref> <ref>PMID:8299698</ref> <ref>PMID:8088810</ref> <ref>PMID:8027558</ref> <ref>PMID:7937790</ref> <ref>PMID:7668284</ref> <ref>PMID:7557965</ref> <ref>PMID:7860773</ref> <ref>PMID:8900089</ref> <ref>PMID:9150740</ref> Defects in IL2RG are the cause of X-linked combined immunodeficiency (XCID) [MIM:[https://omim.org/entry/312863 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.<ref>PMID:7883965</ref> <ref>PMID:9399950</ref>
| + | [https://www.uniprot.org/uniprot/IL2RA_HUMAN IL2RA_HUMAN] Genetic variations in IL2RA are associated with susceptibility to diabetes mellitus insulin-dependent type 10 (IDDM10) [MIM:[https://omim.org/entry/601942 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.<ref>PMID:17676041</ref> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/IL2_HUMAN 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. [[https://www.uniprot.org/uniprot/IL2RA_HUMAN IL2RA_HUMAN]] Receptor for interleukin-2. [[https://www.uniprot.org/uniprot/IL2RG_HUMAN IL2RG_HUMAN]] Common subunit for the receptors for a variety of interleukins. [[https://www.uniprot.org/uniprot/IL2RB_HUMAN IL2RB_HUMAN]] Receptor for interleukin-2. This beta subunit is involved in receptor mediated endocytosis and transduces the mitogenic signals of IL2.
| + | [https://www.uniprot.org/uniprot/IL2RA_HUMAN IL2RA_HUMAN] Receptor for interleukin-2. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Debler, E W]] | + | [[Category: Debler EW]] |
| - | [[Category: Stauber, D J]] | + | [[Category: Stauber DJ]] |
| - | [[Category: Wilson, I A]] | + | [[Category: Wilson IA]] |
| - | [[Category: Immune system-cytokine complex]]
| + | |
| - | [[Category: Interleukin-2]]
| + | |
| - | [[Category: Interleukin-2 alpha receptor]]
| + | |
| - | [[Category: Interleukin-2 beta receptor]]
| + | |
| - | [[Category: Interleukin-2 gamma receptor]]
| + | |
| Structural highlights
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]
Function
IL2RA_HUMAN Receptor for interleukin-2.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
IL-2 is a cytokine that functions as a growth factor and central regulator in the immune system and mediates its effects through ligand-induced hetero-trimerization of the receptor subunits IL-2R alpha, IL-2R beta, and gamma(c). Here, we describe the crystal structure of the trimeric assembly of the human IL-2 receptor ectodomains in complex with IL-2 at 3.0 A resolution. The quaternary structure is consistent with a stepwise assembly from IL-2/IL-2R alpha to IL-2/IL-2R alpha/IL-2R beta to IL-2/IL-2R alpha/IL-2R beta/gamma(c). The IL-2R alpha subunit forms the largest of the three IL-2/IL-2R interfaces, which, together with the high abundance of charge-charge interactions, correlates well with the rapid association rate and high-affinity interaction of IL-2R alpha with IL-2 at the cell surface. Surprisingly, IL-2R alpha makes no contacts with IL-2R beta or gamma(c), and only minor changes are observed in the IL-2 structure in response to receptor binding. These findings support the principal role of IL-2R alpha to deliver IL-2 to the signaling complex and act as regulator of signal transduction. Cooperativity in assembly of the final quaternary complex is easily explained by the extraordinarily extensive set of interfaces found within the fully assembled IL-2 signaling complex, which nearly span the entire length of the IL-2R beta and gamma(c) subunits. Helix A of IL-2 wedges tightly between IL-2R beta and gamma(c) to form a three-way junction that coalesces into a composite binding site for the final gamma(c) recruitment. The IL-2/gamma(c) interface itself exhibits the smallest buried surface and the fewest hydrogen bonds in the complex, which is consistent with its promiscuous use in other cytokine receptor complexes.
Crystal structure of the IL-2 signaling complex: paradigm for a heterotrimeric cytokine receptor.,Stauber DJ, Debler EW, Horton PA, Smith KA, Wilson IA Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2788-93. Epub 2006 Feb 13. PMID:16477002[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ Stauber DJ, Debler EW, Horton PA, Smith KA, Wilson IA. Crystal structure of the IL-2 signaling complex: paradigm for a heterotrimeric cytokine receptor. Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2788-93. Epub 2006 Feb 13. PMID:16477002
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