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| | ==NMR structure of calcium-loaded STIM2 EF-SAM.== | | ==NMR structure of calcium-loaded STIM2 EF-SAM.== |
| - | <StructureSection load='2l5y' size='340' side='right' caption='[[2l5y]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2l5y' size='340' side='right'caption='[[2l5y]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2l5y]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L5Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2L5Y FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2l5y]] 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=2L5Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L5Y FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KIAA1482, STIM2 ([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=CA:CALCIUM+ION'>CA</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=2l5y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l5y OCA], [http://pdbe.org/2l5y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2l5y RCSB], [http://www.ebi.ac.uk/pdbsum/2l5y PDBsum]</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=2l5y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l5y OCA], [https://pdbe.org/2l5y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l5y RCSB], [https://www.ebi.ac.uk/pdbsum/2l5y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l5y ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/STIM2_HUMAN STIM2_HUMAN]] Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores. Functions as a highly sensitive Ca(2+) sensor in the endoplasmic reticulum which activates both store-operated and store-independent Ca(2+)-influx. Regulates basal cytosolic and endoplasmic reticulum Ca(2+) concentrations. Upon mild variations of the endoplasmic reticulum Ca(2+) concentration, translocates from the endoplasmic reticulum to the plasma membrane where it probably activates the Ca(2+) release-activated Ca(2+) (CRAC) channels ORAI1, ORAI2 and ORAI3. May inhibit STIM1-mediated Ca(2+) influx.<ref>PMID:16005298</ref> <ref>PMID:16860747</ref> <ref>PMID:17905723</ref> <ref>PMID:18160041</ref> <ref>PMID:21217057</ref> <ref>PMID:22464749</ref> <ref>PMID:23359669</ref> | + | [https://www.uniprot.org/uniprot/STIM2_HUMAN STIM2_HUMAN] Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores. Functions as a highly sensitive Ca(2+) sensor in the endoplasmic reticulum which activates both store-operated and store-independent Ca(2+)-influx. Regulates basal cytosolic and endoplasmic reticulum Ca(2+) concentrations. Upon mild variations of the endoplasmic reticulum Ca(2+) concentration, translocates from the endoplasmic reticulum to the plasma membrane where it probably activates the Ca(2+) release-activated Ca(2+) (CRAC) channels ORAI1, ORAI2 and ORAI3. May inhibit STIM1-mediated Ca(2+) influx.<ref>PMID:16005298</ref> <ref>PMID:16860747</ref> <ref>PMID:17905723</ref> <ref>PMID:18160041</ref> <ref>PMID:21217057</ref> <ref>PMID:22464749</ref> <ref>PMID:23359669</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Stromal interaction molecules (STIM)s function as endoplasmic reticulum calcium (Ca(2+)) sensors that differentially regulate plasma membrane Ca(2+) release activated Ca(2+) channels in various cells. To probe the structural basis for the functional differences between STIM1 and STIM2 we engineered a series of EF-hand and sterile alpha motif (SAM) domain (EF-SAM) chimeras, demonstrating that the STIM1 Ca(2+)-binding EF-hand and the STIM2 SAM domain are major contributors to the autoinhibition of oligomerization in each respective isoform. Our nuclear magnetic resonance (NMR) derived STIM2 EF-SAM structure provides a rationale for an augmented stability, which involves a 54 degrees pivot in the EF-hand:SAM domain orientation permissible by an expanded nonpolar cleft, ionic interactions, and an enhanced hydrophobic SAM core, unique to STIM2. Live cells expressing "super-unstable" or "super-stable" STIM1/STIM2 EF-SAM chimeras in the full-length context show a remarkable correlation with the in vitro data. Together, our data suggest that divergent Ca(2+)- and SAM-dependent stabilization of the EF-SAM fold contributes to the disparate regulation of store-operated Ca(2+) entry by STIM1 and STIM2.
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| - | Auto-inhibitory role of the EF-SAM domain of STIM proteins in store-operated calcium entry.,Zheng L, Stathopulos PB, Schindl R, Li GY, Romanin C, Ikura M Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1337-42. Epub 2011 Jan 7. PMID:21217057<ref>PMID:21217057</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 2l5y" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Ikura, M]] | + | [[Category: Large Structures]] |
| - | [[Category: Stathopulos, P B]] | + | [[Category: Ikura M]] |
| - | [[Category: Zheng, L]] | + | [[Category: Stathopulos PB]] |
| - | [[Category: Ef-hand]] | + | [[Category: Zheng L]] |
| - | [[Category: Sam domain]]
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| - | [[Category: Signaling protein]]
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| - | [[Category: Store operated calcium entry]]
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| - | [[Category: Stromal interaction molecule]]
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| Structural highlights
Function
STIM2_HUMAN Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores. Functions as a highly sensitive Ca(2+) sensor in the endoplasmic reticulum which activates both store-operated and store-independent Ca(2+)-influx. Regulates basal cytosolic and endoplasmic reticulum Ca(2+) concentrations. Upon mild variations of the endoplasmic reticulum Ca(2+) concentration, translocates from the endoplasmic reticulum to the plasma membrane where it probably activates the Ca(2+) release-activated Ca(2+) (CRAC) channels ORAI1, ORAI2 and ORAI3. May inhibit STIM1-mediated Ca(2+) influx.[1] [2] [3] [4] [5] [6] [7]
References
- ↑ Liou J, Kim ML, Heo WD, Jones JT, Myers JW, Ferrell JE Jr, Meyer T. STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx. Curr Biol. 2005 Jul 12;15(13):1235-41. PMID:16005298 doi:10.1016/j.cub.2005.05.055
- ↑ Soboloff J, Spassova MA, Hewavitharana T, He LP, Xu W, Johnstone LS, Dziadek MA, Gill DL. STIM2 is an inhibitor of STIM1-mediated store-operated Ca2+ Entry. Curr Biol. 2006 Jul 25;16(14):1465-70. PMID:16860747 doi:http://dx.doi.org/S0960-9822(06)01634-4
- ↑ Parvez S, Beck A, Peinelt C, Soboloff J, Lis A, Monteilh-Zoller M, Gill DL, Fleig A, Penner R. STIM2 protein mediates distinct store-dependent and store-independent modes of CRAC channel activation. FASEB J. 2008 Mar;22(3):752-61. Epub 2007 Sep 28. PMID:17905723 doi:http://dx.doi.org/fj.07-9449com
- ↑ Brandman O, Liou J, Park WS, Meyer T. STIM2 is a feedback regulator that stabilizes basal cytosolic and endoplasmic reticulum Ca2+ levels. Cell. 2007 Dec 28;131(7):1327-39. PMID:18160041 doi:http://dx.doi.org/10.1016/j.cell.2007.11.039
- ↑ Zheng L, Stathopulos PB, Schindl R, Li GY, Romanin C, Ikura M. Auto-inhibitory role of the EF-SAM domain of STIM proteins in store-operated calcium entry. Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1337-42. Epub 2011 Jan 7. PMID:21217057 doi:10.1073/pnas.1015125108
- ↑ Palty R, Raveh A, Kaminsky I, Meller R, Reuveny E. SARAF inactivates the store operated calcium entry machinery to prevent excess calcium refilling. Cell. 2012 Apr 13;149(2):425-38. doi: 10.1016/j.cell.2012.01.055. Epub 2012 Mar, 29. PMID:22464749 doi:10.1016/j.cell.2012.01.055
- ↑ Thiel M, Lis A, Penner R. STIM2 drives Ca2+ oscillations through store-operated Ca2+ entry caused by mild store depletion. J Physiol. 2013 Mar 15;591(Pt 6):1433-45. doi: 10.1113/jphysiol.2012.245399. Epub, 2013 Jan 28. PMID:23359669 doi:http://dx.doi.org/10.1113/jphysiol.2012.245399
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