Proteopedia

2l5y

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NMR structure of calcium-loaded STIM2 EF-SAM.NMR structure of calcium-loaded STIM2 EF-SAM.

Structural highlights

2l5y is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:KIAA1482, STIM2 (Homo sapiens)
Resources:FirstGlance, OCA, RCSB, PDBsum

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]

Publication Abstract from PubMed

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.

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[8]

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

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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
  6. ↑ 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
  7. ↑ 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
  8. ↑ 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
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