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| | <StructureSection load='6o2u' size='340' side='right'caption='[[6o2u]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='6o2u' size='340' side='right'caption='[[6o2u]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6o2u]] is a 2 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=6O2U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6O2U FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6o2u]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O2U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O2U FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SARAF, TMEM66, XTP3, HSPC035, NPD003, PSEC0019, UNQ1967/PRO4499 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</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=6o2u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o2u OCA], [http://pdbe.org/6o2u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o2u RCSB], [http://www.ebi.ac.uk/pdbsum/6o2u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o2u 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=6o2u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o2u OCA], [https://pdbe.org/6o2u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6o2u RCSB], [https://www.ebi.ac.uk/pdbsum/6o2u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6o2u ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SARAF_HUMAN SARAF_HUMAN]] Negative regulator of store-operated Ca(2+) entry (SOCE) involved in protecting cells from Ca(2+) overfilling. In response to cytosolic Ca(2+) elevation after endoplasmic reticulum Ca(2+) refilling, promotes a slow inactivation of STIM (STIM1 or STIM2)-dependent SOCE activity: possibly act by facilitating the deoligomerization of STIM to efficiently turn off ORAI when the endoplasmic reticulum lumen is filled with the appropriate Ca(2+) levels, and thus preventing the overload of the cell with excessive Ca(2+) ions.<ref>PMID:22464749</ref> | + | [https://www.uniprot.org/uniprot/SARAF_HUMAN SARAF_HUMAN] Negative regulator of store-operated Ca(2+) entry (SOCE) involved in protecting cells from Ca(2+) overfilling. In response to cytosolic Ca(2+) elevation after endoplasmic reticulum Ca(2+) refilling, promotes a slow inactivation of STIM (STIM1 or STIM2)-dependent SOCE activity: possibly act by facilitating the deoligomerization of STIM to efficiently turn off ORAI when the endoplasmic reticulum lumen is filled with the appropriate Ca(2+) levels, and thus preventing the overload of the cell with excessive Ca(2+) ions.<ref>PMID:22464749</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kimberlin, C R]] | + | [[Category: Kimberlin CR]] |
| - | [[Category: Minor, D L]] | + | [[Category: Minor DL]] |
| - | [[Category: Calcium signaling]]
| + | |
| - | [[Category: Domain swap]]
| + | |
| - | [[Category: Endoplasmic reticulum]]
| + | |
| - | [[Category: Er]]
| + | |
| - | [[Category: Saraf]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Soce]]
| + | |
| - | [[Category: Store operated calcium entry]]
| + | |
| Structural highlights
Function
SARAF_HUMAN Negative regulator of store-operated Ca(2+) entry (SOCE) involved in protecting cells from Ca(2+) overfilling. In response to cytosolic Ca(2+) elevation after endoplasmic reticulum Ca(2+) refilling, promotes a slow inactivation of STIM (STIM1 or STIM2)-dependent SOCE activity: possibly act by facilitating the deoligomerization of STIM to efficiently turn off ORAI when the endoplasmic reticulum lumen is filled with the appropriate Ca(2+) levels, and thus preventing the overload of the cell with excessive Ca(2+) ions.[1]
Publication Abstract from PubMed
Store-Operated Calcium Entry (SOCE) plays key roles in cell proliferation, muscle contraction, immune responses, and memory formation. The coordinated interactions of a number of proteins from the plasma and endoplasmic reticulum membranes control SOCE to replenish internal Ca(2+) stores and generate intracellular Ca(2+) signals. SARAF, an endoplasmic reticulum resident component of the SOCE pathway having no homology to any characterized protein, serves as an important brake on SOCE. Here, we describe the X-ray crystal structure of the SARAF luminal domain, SARAFL. This domain forms a novel 10-stranded beta-sandwich fold that includes a set of three conserved disulfide bonds, denoted the "SARAF-fold." The structure reveals a domain-swapped dimer in which the last two beta-strands (beta9 and beta10) are exchanged forming a region denoted the "SARAF luminal switch" that is essential for dimerization. Sequence comparisons reveal that the SARAF-fold is highly conserved in vertebrates and in a variety of pathologic fungi. Forster resonance energy transfer experiments using full-length SARAF validate the formation of the domain-swapped dimer in cells and demonstrate that dimerization is reversible. A designed variant lacking the SARAF luminal switch shows that the domain swapping is essential to function and indicates that the SARAF dimer accelerates SOCE inactivation.
SARAF Luminal Domain Structure Reveals a Novel Domain-Swapped beta-Sandwich Fold Important for SOCE Modulation.,Kimberlin CR, Meshcheriakova A, Palty R, Raveh A, Karbat I, Reuveny E, Minor DL Jr J Mol Biol. 2019 May 11. pii: S0022-2836(19)30263-3. doi:, 10.1016/j.jmb.2019.05.008. PMID:31082439[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ Kimberlin CR, Meshcheriakova A, Palty R, Raveh A, Karbat I, Reuveny E, Minor DL Jr. SARAF Luminal Domain Structure Reveals a Novel Domain-Swapped beta-Sandwich Fold Important for SOCE Modulation. J Mol Biol. 2019 May 11. pii: S0022-2836(19)30263-3. doi:, 10.1016/j.jmb.2019.05.008. PMID:31082439 doi:http://dx.doi.org/10.1016/j.jmb.2019.05.008
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