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| | ==Crystal structure of Interleukin 15 in complex with Interleukin 15 receptor alpha== | | ==Crystal structure of Interleukin 15 in complex with Interleukin 15 receptor alpha== |
| - | <StructureSection load='2psm' size='340' side='right' caption='[[2psm]], [[Resolution|resolution]] 2.19Å' scene=''> | + | <StructureSection load='2psm' size='340' side='right'caption='[[2psm]], [[Resolution|resolution]] 2.19Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2psm]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PSM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2PSM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2psm]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PSM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PSM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BAM:BENZAMIDINE'>BAM</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BAM:BENZAMIDINE'>BAM</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Il15 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Il15ra ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Il15 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Il15ra ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=2psm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2psm OCA], [http://pdbe.org/2psm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2psm RCSB], [http://www.ebi.ac.uk/pdbsum/2psm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2psm ProSAT], [http://www.topsan.org/Proteins/RSGI/2psm TOPSAN]</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=2psm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2psm OCA], [https://pdbe.org/2psm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2psm RCSB], [https://www.ebi.ac.uk/pdbsum/2psm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2psm ProSAT], [https://www.topsan.org/Proteins/RSGI/2psm TOPSAN]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IL15_MOUSE IL15_MOUSE]] 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/I15RA_MOUSE I15RA_MOUSE]] 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. Signal transduction seems to involve STAT3, STAT5, STAT6, JAK2 and SYK. Expression of different isoforms may alter or interfere with signal transduction.<ref>PMID:12734349</ref> <ref>PMID:17947230</ref> | + | [[https://www.uniprot.org/uniprot/IL15_MOUSE IL15_MOUSE]] 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. [[https://www.uniprot.org/uniprot/I15RA_MOUSE I15RA_MOUSE]] 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. Signal transduction seems to involve STAT3, STAT5, STAT6, JAK2 and SYK. Expression of different isoforms may alter or interfere with signal transduction.<ref>PMID:12734349</ref> <ref>PMID:17947230</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Interleukin|Interleukin]] | + | *[[Interleukin 3D structures|Interleukin 3D structures]] |
| - | *[[Interleukin receptor|Interleukin receptor]] | + | *[[Interleukin receptor 3D structures|Interleukin receptor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Lk3 transgenic mice]] | | [[Category: Lk3 transgenic mice]] |
| | [[Category: Kanagawa, O]] | | [[Category: Kanagawa, O]] |
| Structural highlights
Function
[IL15_MOUSE] 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. [I15RA_MOUSE] 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. Signal transduction seems to involve STAT3, STAT5, STAT6, JAK2 and SYK. Expression of different isoforms may alter or interfere with signal transduction.[1] [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
Interleukin (IL)-15 is a pleiotropic cytokine that plays a pivotal role in both innate and adaptive immunity. IL-15 is unique among cytokines due to its participation in a trans signaling mechanism in which IL-15 receptor alpha (IL-15Ralpha) from one subset of cells presents IL-15 to neighboring IL-2Rbeta/gammac-expressing cells. Here we present the crystal structure of IL-15 in complex with the sushi domain of IL-15Ralpha. The structure reveals that the alpha receptor-binding epitope of IL-15 adopts a unique conformation, which, together with amino acid substitutions, permits specific interactions with IL-15Ralpha that account for the exceptionally high affinity of the IL-15.IL-15Ralpha complex. Interestingly, analysis of the topology of IL-15 and IL-15Ralpha at the IL-15.IL-15Ralpha interface suggests that IL-15 should be capable of participating in a cis signaling mechanism similar to that of the related cytokine IL-2. Indeed, we present biochemical data demonstrating that IL-15 is capable of efficiently signaling in cis through IL-15Ralpha and IL-2Rbeta/gammac expressed on the surface of a single cell. Based on our data we propose that cis presentation of IL-15 may be important in certain biological contexts and that flexibility of IL-15Ralpha permits IL-15 and its three receptor components to be assembled identically at the ligand-receptor interface whether IL-15 is presented in cis or trans. Finally, we have gained insights into IL-15.IL-15Ralpha.IL-2Rbeta.gammac quaternary complex assembly through the use of molecular modeling.
Crystal Structure of the interleukin-15.interleukin-15 receptor alpha complex: insights into trans and cis presentation.,Olsen SK, Ota N, Kishishita S, Kukimoto-Niino M, Murayama K, Uchiyama H, Toyama M, Terada T, Shirouzu M, Kanagawa O, Yokoyama S J Biol Chem. 2007 Dec 21;282(51):37191-204. Epub 2007 Oct 18. PMID:17947230[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bulanova E, Budagian V, Orinska Z, Krause H, Paus R, Bulfone-Paus S. Mast cells express novel functional IL-15 receptor alpha isoforms. J Immunol. 2003 May 15;170(10):5045-55. PMID:12734349
- ↑ Olsen SK, Ota N, Kishishita S, Kukimoto-Niino M, Murayama K, Uchiyama H, Toyama M, Terada T, Shirouzu M, Kanagawa O, Yokoyama S. Crystal Structure of the interleukin-15.interleukin-15 receptor alpha complex: insights into trans and cis presentation. J Biol Chem. 2007 Dec 21;282(51):37191-204. Epub 2007 Oct 18. PMID:17947230 doi:10.1074/jbc.M706150200
- ↑ Olsen SK, Ota N, Kishishita S, Kukimoto-Niino M, Murayama K, Uchiyama H, Toyama M, Terada T, Shirouzu M, Kanagawa O, Yokoyama S. Crystal Structure of the interleukin-15.interleukin-15 receptor alpha complex: insights into trans and cis presentation. J Biol Chem. 2007 Dec 21;282(51):37191-204. Epub 2007 Oct 18. PMID:17947230 doi:10.1074/jbc.M706150200
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