|
|
| Line 3: |
Line 3: |
| <StructureSection load='6yel' size='340' side='right'caption='[[6yel]]' scene=''> | | <StructureSection load='6yel' size='340' side='right'caption='[[6yel]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6yel]] 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=6YEL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YEL FirstGlance]. <br> | | <table><tr><td colspan='2'>Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YEL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YEL FirstGlance]. <br> |
| </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=6yel FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yel OCA], [https://pdbe.org/6yel PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yel RCSB], [https://www.ebi.ac.uk/pdbsum/6yel PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yel ProSAT]</span></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6yel FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yel OCA], [https://pdbe.org/6yel PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yel RCSB], [https://www.ebi.ac.uk/pdbsum/6yel PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yel ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Disease ==
| |
| [https://www.uniprot.org/uniprot/STIM1_HUMAN STIM1_HUMAN] Defects in STIM1 are the cause of immune dysfunction with T-cell inactivation due to calcium entry defect type 2 (IDTICED2) [MIM:[https://omim.org/entry/612783 612783]. IDTICED2 is an immune disorder characterized by recurrent infections, impaired T-cell activation and proliferative response, decreased T-cell production of cytokines, lymphadenopathy, and normal lymphocytes counts and serum immunoglobulin levels. Additional features include thrombocytopenia, autoimmune hemolytic anemia, non-progressive myopathy, partial iris hypoplasia, hepatosplenomegaly and defective enamel dentition.<ref>PMID:19420366</ref>
| |
| == Function ==
| |
| [https://www.uniprot.org/uniprot/STIM1_HUMAN STIM1_HUMAN] Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores. Acts as Ca(2+) sensor in the endoplasmic reticulum via its EF-hand domain. Upon Ca(2+) depletion, translocates from the endoplasmic reticulum to the plasma membrane where it activates the Ca(2+) release-activated Ca(2+) (CRAC) channel subunit, TMEM142A/ORAI1.<ref>PMID:9377559</ref> <ref>PMID:16005298</ref> <ref>PMID:15866891</ref> <ref>PMID:16208375</ref> <ref>PMID:16807233</ref> <ref>PMID:16766533</ref> <ref>PMID:16733527</ref> <ref>PMID:16537481</ref> <ref>PMID:22464749</ref>
| |
| <div style="background-color:#fffaf0;">
| |
| == Publication Abstract from PubMed ==
| |
| The calcium release activated calcium channel is activated by the endoplasmic reticulum-resident calcium sensor protein STIM1. On activation, STIM1 C terminus changes from an inactive, tight to an active, extended conformation. A coiled-coil clamp involving the CC1 and CC3 domains is essential in controlling STIM1 activation, with CC1 as the key entity. The nuclear magnetic resonance-derived solution structure of the CC1 domain represents a three-helix bundle stabilized by interhelical contacts, which are absent in the Stormorken disease-related STIM1 R304W mutant. Two interhelical sites between the CC1alpha1 and CC1alpha2 helices are key in controlling STIM1 activation, affecting the balance between tight and extended conformations. Nuclear magnetic resonance-directed mutations within these interhelical interactions restore the physiological, store-dependent activation behavior of the gain-of-function STIM1 R304W mutant. This study reveals the functional impact of interhelical interactions within the CC1 domain for modifying the CC1-CC3 clamp strength to control the activation of STIM1.
| |
|
| |
| Interhelical interactions within the STIM1 CC1 domain modulate CRAC channel activation.,Rathner P, Fahrner M, Cerofolini L, Grabmayr H, Horvath F, Krobath H, Gupta A, Ravera E, Fragai M, Bechmann M, Renger T, Luchinat C, Romanin C, Muller N Nat Chem Biol. 2020 Oct 26. pii: 10.1038/s41589-020-00672-8. doi:, 10.1038/s41589-020-00672-8. PMID:33106661<ref>PMID:33106661</ref>
| |
|
| |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| |
| </div>
| |
| <div class="pdbe-citations 6yel" style="background-color:#fffaf0;"></div>
| |
| == References ==
| |
| <references/>
| |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Homo sapiens]]
| |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Bechmann M]] | | [[Category: Bechmann M]] |