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{{STRUCTURE_2b5i|  PDB=2b5i  |  SCENE=  }}
===cytokine receptor complex===
{{ABSTRACT_PUBMED_16293754}}


==Disease==
==cytokine receptor complex==
[[http://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:[http://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> [[http://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. [[http://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:[http://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:[http://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>
<StructureSection load='2b5i' size='340' side='right'caption='[[2b5i]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2b5i]] is a 4 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=2B5I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2B5I FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=2b5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b5i OCA], [https://pdbe.org/2b5i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2b5i RCSB], [https://www.ebi.ac.uk/pdbsum/2b5i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2b5i ProSAT]</span></td></tr>
</table>
== Function ==
[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.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b5/2b5i_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2b5i ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Interleukin-2 (IL-2) is an immunoregulatory cytokine that acts through a quaternary receptor signaling complex containing alpha (IL-2Ralpha), beta (IL-2Rbeta), and common gamma chain (gc) receptors. In the structure of the quaternary ectodomain complex as visualized at a resolution of 2.3 angstroms, the binding of IL-2Ralpha to IL-2 stabilizes a secondary binding site for presentation to IL-2Rbeta. gammac is then recruited to the composite surface formed by the IL-2/IL-2Rbeta complex. Consistent with its role as a shared receptor for IL-4, IL-7, IL-9, IL-15, and IL-21, gammac forms degenerate contacts with IL-2. The structure of gammac provides a rationale for loss-of-function mutations found in patients with X-linked severe combined immunodeficiency diseases (X-SCID). This complex structure provides a framework for other gammac-dependent cytokine-receptor interactions and for the engineering of improved IL-2 therapeutics.


==Function==
Structure of the quaternary complex of interleukin-2 with its alpha, beta, and gammac receptors.,Wang X, Rickert M, Garcia KC Science. 2005 Nov 18;310(5751):1159-63. PMID:16293754<ref>PMID:16293754</ref>
[[http://www.uniprot.org/uniprot/IL2RA_HUMAN IL2RA_HUMAN]] Receptor for interleukin-2. [[http://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. [[http://www.uniprot.org/uniprot/IL2RG_HUMAN IL2RG_HUMAN]] Common subunit for the receptors for a variety of interleukins. [[http://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.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[2b5i]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2B5I OCA].
</div>
<div class="pdbe-citations 2b5i" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Interleukin|Interleukin]]
*[[Interleukin 3D structures|Interleukin 3D structures]]
*[[Interleukin receptor|Interleukin receptor]]
*[[Interleukin receptor|Interleukin receptor]]
 
*[[Interleukin receptor 3D structures|Interleukin receptor 3D structures]]
==Reference==
== References ==
<ref group="xtra">PMID:016293754</ref><references group="xtra"/><references/>
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Garcia, K C.]]
[[Category: Large Structures]]
[[Category: Rickert, M.]]
[[Category: Garcia KC]]
[[Category: Wang, X.]]
[[Category: Rickert M]]
[[Category: Cytokine-cytokine receptor complex]]
[[Category: Wang X]]
[[Category: Fibronectin domain]]
[[Category: Four-helix bundle]]

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