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| ==ASPECTS OF RECEPTOR BINDING AND SIGNALLING OF INTERLEUKIN-4 INVESTIGATED BY SITE-DIRECTED MUTAGENESIS AND NMR SPECTROSCOPY== | | ==ASPECTS OF RECEPTOR BINDING AND SIGNALLING OF INTERLEUKIN-4 INVESTIGATED BY SITE-DIRECTED MUTAGENESIS AND NMR SPECTROSCOPY== |
- | <StructureSection load='2cyk' size='340' side='right'caption='[[2cyk]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | + | <StructureSection load='2cyk' size='340' side='right'caption='[[2cyk]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[2cyk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CYK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CYK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2cyk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CYK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CYK FirstGlance]. <br> |
- | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1cyl|1cyl]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2cyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cyk OCA], [https://pdbe.org/2cyk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cyk RCSB], [https://www.ebi.ac.uk/pdbsum/2cyk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cyk 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=2cyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cyk OCA], [https://pdbe.org/2cyk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cyk RCSB], [https://www.ebi.ac.uk/pdbsum/2cyk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cyk ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Disease == | | == Disease == |
- | [[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>
| + | [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 == |
- | [[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.
| + | [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. |
| == 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: Mueller, T]] | + | [[Category: Mueller T]] |
- | [[Category: Oschkinat, H]] | + | [[Category: Oschkinat H]] |
- | [[Category: Sebald, W]] | + | [[Category: Sebald W]] |
- | [[Category: Cytokine]]
| + | |
| 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.
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
Cytokines are hormones that carry information from cell to cell. This information is read from their surface upon binding to transmembrane receptors and by the subsequent initiation of receptor oligomerization. An influence on this process through mutagenesis on the hormone surface is highly desirable for medical reasons. However, an understanding of hormone-receptor interactions requires insight into the structural changes introduced by the mutations. In this line structural studies on human IL-4 and the medically important IL-4 antagonists Y124D and Y124G are presented. The site around Y124 is an important epitope responsible for the ability of IL-4 to cause a signal in the target cells. It is shown that the local main-chain structure around residue 124 in the variants remains unchanged. A strategy is presented here which allows the study of these types of proteins and their variants by NMR which does not require carbon labelled samples.
Aspects of receptor binding and signalling of interleukin-4 investigated by site-directed mutagenesis and NMR spectroscopy.,Muller T, Dieckmann T, Sebald W, Oschkinat H J Mol Biol. 1994 Apr 8;237(4):423-36. PMID:8151703[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
- ↑ Muller T, Dieckmann T, Sebald W, Oschkinat H. Aspects of receptor binding and signalling of interleukin-4 investigated by site-directed mutagenesis and NMR spectroscopy. J Mol Biol. 1994 Apr 8;237(4):423-36. PMID:8151703 doi:http://dx.doi.org/10.1006/jmbi.1994.1245
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