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| | ==Interleukin-4 mutant RGA bound to cytokine receptor common gamma== | | ==Interleukin-4 mutant RGA bound to cytokine receptor common gamma== |
| - | <StructureSection load='3qb7' size='340' side='right' caption='[[3qb7]], [[Resolution|resolution]] 3.25Å' scene=''> | + | <StructureSection load='3qb7' size='340' side='right'caption='[[3qb7]], [[Resolution|resolution]] 3.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3qb7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QB7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QB7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3qb7]] 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=3QB7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QB7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 3.245Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IL2RG ([http://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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3qb7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qb7 OCA], [http://pdbe.org/3qb7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3qb7 RCSB], [http://www.ebi.ac.uk/pdbsum/3qb7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3qb7 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=3qb7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qb7 OCA], [https://pdbe.org/3qb7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qb7 RCSB], [https://www.ebi.ac.uk/pdbsum/3qb7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qb7 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[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> | + | [https://www.uniprot.org/uniprot/IL4_HUMAN IL4_HUMAN] Genetic variations in IL4 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:[https://omim.org/entry/601367 601367]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.<ref>PMID:14681304</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IL2RG_HUMAN IL2RG_HUMAN]] Common subunit for the receptors for a variety of interleukins. | + | [https://www.uniprot.org/uniprot/IL4_HUMAN IL4_HUMAN] Participates in at least several B-cell activation processes as well as of other cell types. It is a costimulator of DNA-synthesis. It induces the expression of class II MHC molecules on resting B-cells. It enhances both secretion and cell surface expression of IgE and IgG1. It also regulates the expression of the low affinity Fc receptor for IgE (CD23) on both lymphocytes and monocytes. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Interleukin|Interleukin]] | + | *[[Interleukin 3D structures|Interleukin 3D structures]] |
| | + | *[[Interleukin receptor 3D structures|Interleukin receptor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bates, D L]] | + | [[Category: Large Structures]] |
| - | [[Category: Creusot, R J]] | + | [[Category: Bates DL]] |
| - | [[Category: Fathman, C G]] | + | [[Category: Creusot RJ]] |
| - | [[Category: Garcia, K C]] | + | [[Category: Fathman CG]] |
| - | [[Category: Junttila, I S]] | + | [[Category: Garcia KC]] |
| - | [[Category: Lupardus, P]] | + | [[Category: Junttila IS]] |
| - | [[Category: Moraga, I]] | + | [[Category: Lupardus P]] |
| - | [[Category: Paul, W E]] | + | [[Category: Moraga I]] |
| - | [[Category: Cytokine signaling]]
| + | [[Category: Paul WE]] |
| - | [[Category: Cytokine-cytokine receptor complex]]
| + | |
| - | [[Category: Il-4ralpha]]
| + | |
| Structural highlights
Disease
IL4_HUMAN Genetic variations in IL4 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:601367; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.[1]
Function
IL4_HUMAN Participates in at least several B-cell activation processes as well as of other cell types. It is a costimulator of DNA-synthesis. It induces the expression of class II MHC molecules on resting B-cells. It enhances both secretion and cell surface expression of IgE and IgG1. It also regulates the expression of the low affinity Fc receptor for IgE (CD23) on both lymphocytes and monocytes.
Publication Abstract from PubMed
Cytokines dimerize their receptors, with the binding of the 'second chain' triggering signaling. In the interleukin (IL)-4 and IL-13 system, different cell types express varying numbers of alternative second receptor chains (gammac or IL-13Ralpha1), forming functionally distinct type I or type II complexes. We manipulated the affinity and specificity of second chain recruitment by human IL-4. A type I receptor-selective IL-4 'superkine' with 3,700-fold higher affinity for gammac was three- to ten-fold more potent than wild-type IL-4. Conversely, a variant with high affinity for IL-13Ralpha1 more potently activated cells expressing the type II receptor and induced differentiation of dendritic cells from monocytes, implicating the type II receptor in this process. Superkines showed signaling advantages on cells with lower second chain numbers. Comparative transcriptional analysis reveals that the superkines induce largely redundant gene expression profiles. Variable second chain numbers can be exploited to redirect cytokines toward distinct cell subsets and elicit new actions, potentially improving the selectivity of cytokine therapy.
Redirecting cell-type specific cytokine responses with engineered interleukin-4 superkines.,Junttila IS, Creusot RJ, Moraga I, Bates DL, Wong MT, Alonso MN, Suhoski MM, Lupardus P, Meier-Schellersheim M, Engleman EG, Utz PJ, Fathman CG, Paul WE, Garcia KC Nat Chem Biol. 2012 Oct 28. doi: 10.1038/nchembio.1096. PMID:23103943[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zee RY, Cook NR, Cheng S, Reynolds R, Erlich HA, Lindpaintner K, Ridker PM. Polymorphism in the P-selectin and interleukin-4 genes as determinants of stroke: a population-based, prospective genetic analysis. Hum Mol Genet. 2004 Feb 15;13(4):389-96. Epub 2003 Dec 17. PMID:14681304 doi:10.1093/hmg/ddh039
- ↑ Junttila IS, Creusot RJ, Moraga I, Bates DL, Wong MT, Alonso MN, Suhoski MM, Lupardus P, Meier-Schellersheim M, Engleman EG, Utz PJ, Fathman CG, Paul WE, Garcia KC. Redirecting cell-type specific cytokine responses with engineered interleukin-4 superkines. Nat Chem Biol. 2012 Oct 28. doi: 10.1038/nchembio.1096. PMID:23103943 doi:http://dx.doi.org/10.1038/nchembio.1096
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