4gs7: Difference between revisions

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-{{STRUCTURE_4gs7|  PDB=4gs7  |  SCENE=  }}
-===Structure of the Interleukin-15 quaternary complex===
-{{ABSTRACT_PUBMED_23104097}}
-==Disease==
+==Structure of the Interleukin-15 quaternary complex==
-[[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='4gs7' size='340' side='right'caption='[[4gs7]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4gs7]] 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=4GS7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GS7 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</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=4gs7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gs7 OCA], [https://pdbe.org/4gs7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gs7 RCSB], [https://www.ebi.ac.uk/pdbsum/4gs7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gs7 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/IL15_HUMAN IL15_HUMAN] Cytokine that stimulates the proliferation of T-lymphocytes. Stimulation by IL-15 requires interaction of IL-15 with components of IL-2R, including IL-2R beta and probably IL-2R gamma but not IL-2R alpha.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Interleukin 15 (IL-15) and IL-2 have distinct immunological functions even though both signal through the receptor subunit IL-2Rbeta and the common gamma-chain (gamma(c)). Here we found that in the structure of the IL-15-IL-15Ralpha-IL-2Rbeta-gamma(c) quaternary complex, IL-15 binds to IL-2Rbeta and gamma(c) in a heterodimer nearly indistinguishable from that of the IL-2-IL-2Ralpha-IL-2Rbeta-gamma(c) complex, despite their different receptor-binding chemistries. IL-15Ralpha substantially increased the affinity of IL-15 for IL-2Rbeta, and this allostery was required for IL-15 trans signaling. Consistent with their identical IL-2Rbeta-gamma(c) dimer geometries, IL-2 and IL-15 showed similar signaling properties in lymphocytes, with any differences resulting from disparate receptor affinities. Thus, IL-15 and IL-2 induced similar signals, and the cytokine specificity of IL-2Ralpha versus IL-15Ralpha determined cellular responsiveness. Our results provide new insights for the development of specific immunotherapeutics based on IL-15 or IL-2.
-==Function==
+Mechanistic and structural insight into the functional dichotomy between IL-2 and IL-15.,Ring AM, Lin JX, Feng D, Mitra S, Rickert M, Bowman GR, Pande VS, Li P, Moraga I, Spolski R, Ozkan E, Leonard WJ, Garcia KC Nat Immunol. 2012 Oct 28. doi: 10.1038/ni.2449. PMID:23104097<ref>PMID:23104097</ref>
-[[http://www.uniprot.org/uniprot/I15RA_HUMAN I15RA_HUMAN]] High-affinity receptor for interleukin-15. Can signal both in cis and trans where IL15R from one subset of cells presents IL15 to neighboring IL2RG-expressing cells. Expression of different isoforms may alter or interfere with signal transduction. Isoform 5, isoform 6, isoform 7 and isoform 8 do not bind IL15. Signal transduction involves STAT3, STAT5, STAT6, JAK2 (By similarity) and SYK.<ref>PMID:8530383</ref><ref>PMID:11714793</ref> [[http://www.uniprot.org/uniprot/IL15_HUMAN IL15_HUMAN]] Cytokine that stimulates the proliferation of T-lymphocytes. Stimulation by IL-15 requires interaction of IL-15 with components of IL-2R, including IL-2R beta and probably IL-2R gamma but not IL-2R alpha. [[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>
-[[4gs7]] 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=4GS7 OCA].
+</div>
+<div class="pdbe-citations 4gs7" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-<references group="xtra"/><references/>
+*[[Interleukin 3D structures|Interleukin 3D structures]]
+*[[Interleukin receptor 3D structures|Interleukin receptor 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Feng, D.]]
+[[Category: Large Structures]]
-[[Category: Garcia, K C.]]
+[[Category: Feng D]]
-[[Category: Ozkan, E.]]
+[[Category: Garcia KC]]
-[[Category: Ring, A M.]]
+[[Category: Ozkan E]]
-[[Category: Anti-tumor]]
+[[Category: Ring AM]]
-[[Category: Anti-viral]]
-[[Category: Cytokine]]
-[[Category: Cytokine receptor]]
-[[Category: Immune system]]
-[[Category: Immunoregulatory]]
-[[Category: Reductive methylation]]