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==Crystal structure of the IL-15/IL-15Ra complex==
==Crystal structure of the IL-15/IL-15Ra complex==
<StructureSection load='2z3q' size='340' side='right' caption='[[2z3q]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
<StructureSection load='2z3q' size='340' side='right'caption='[[2z3q]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2z3q]] 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=2Z3Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Z3Q FirstGlance]. <br>
<table><tr><td colspan='2'>[[2z3q]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Z3Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Z3Q FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2z3r|2z3r]]</td></tr>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2z3r|2z3r]]</div></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=9606 HUMAN]), IL15RA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=9606 HUMAN]), IL15RA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2z3q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z3q OCA], [http://pdbe.org/2z3q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2z3q RCSB], [http://www.ebi.ac.uk/pdbsum/2z3q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2z3q 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=2z3q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z3q OCA], [https://pdbe.org/2z3q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2z3q RCSB], [https://www.ebi.ac.uk/pdbsum/2z3q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2z3q ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[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/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>   
[[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. [[https://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>   
== 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/>
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</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Chirifu, M]]
[[Category: Chirifu, M]]
[[Category: Davis, S J]]
[[Category: Davis, S J]]

Revision as of 13:45, 8 December 2021

Crystal structure of the IL-15/IL-15Ra complexCrystal structure of the IL-15/IL-15Ra complex

Structural highlights

2z3q is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:IL15 (HUMAN), IL15RA (HUMAN)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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. [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.[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 15 (IL-15) and IL-2, which promote the survival of memory CD8(+) T cells and regulatory T cells, respectively, bind receptor complexes that share beta- and gamma-signaling subunits. Receptor specificity is provided by unique, nonsignaling alpha-subunits. Whereas IL-2 receptor-alpha (IL-2Ralpha) is expressed together in cis with the beta- and gamma-subunits on T cells and B cells, IL-15Ralpha is expressed in trans on antigen-presenting cells. Here we present a 1.85-A crystal structure of the human IL-15-IL-15Ralpha complex. The structure provides insight into the molecular basis of the specificity of cytokine recognition and emphasizes the importance of water in generating this very high-affinity complex. Despite very low IL-15-IL-2 sequence homology and distinct receptor architecture, the topologies of the IL-15-IL-15Ralpha and IL-2-IL-2Ralpha complexes are very similar. Our data raise the possibility that IL-2, like IL-15, might be capable of being presented in trans in the context of its unique receptor alpha-chain.

Crystal structure of the IL-15-IL-15Ralpha complex, a cytokine-receptor unit presented in trans.,Chirifu M, Hayashi C, Nakamura T, Toma S, Shuto T, Kai H, Yamagata Y, Davis SJ, Ikemizu S Nat Immunol. 2007 Sep;8(9):1001-7. Epub 2007 Jul 22. PMID:17643103[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Anderson DM, Kumaki S, Ahdieh M, Bertles J, Tometsko M, Loomis A, Giri J, Copeland NG, Gilbert DJ, Jenkins NA, et al.. Functional characterization of the human interleukin-15 receptor alpha chain and close linkage of IL15RA and IL2RA genes. J Biol Chem. 1995 Dec 15;270(50):29862-9. PMID:8530383
  2. Bulanova E, Budagian V, Pohl T, Krause H, Durkop H, Paus R, Bulfone-Paus S. The IL-15R alpha chain signals through association with Syk in human B cells. J Immunol. 2001 Dec 1;167(11):6292-302. PMID:11714793
  3. Chirifu M, Hayashi C, Nakamura T, Toma S, Shuto T, Kai H, Yamagata Y, Davis SJ, Ikemizu S. Crystal structure of the IL-15-IL-15Ralpha complex, a cytokine-receptor unit presented in trans. Nat Immunol. 2007 Sep;8(9):1001-7. Epub 2007 Jul 22. PMID:17643103 doi:10.1038/ni1492

2z3q, resolution 1.85Å

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