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2mak
From Proteopedia
(Difference between revisions)
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| - | + | ==Solution structure of the STIM1 CC1-CC2 homodimer in complex with two Orai1 C-terminal domains.== | |
| - | + | <StructureSection load='2mak' size='340' side='right' caption='[[2mak]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[2mak]] is a 4 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=2MAK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MAK FirstGlance]. <br> | |
| - | ==Disease== | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2maj|2maj]]</td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">STIM1, GOK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ORAI1, CRACM1, TMEM142A ([http://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=2mak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mak OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2mak RCSB], [http://www.ebi.ac.uk/pdbsum/2mak PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
[[http://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:[http://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> [[http://www.uniprot.org/uniprot/CRCM1_HUMAN CRCM1_HUMAN]] Combined immunodeficiency due to ORAI1 deficiency. The disease is caused by mutations affecting the gene represented in this entry. | [[http://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:[http://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> [[http://www.uniprot.org/uniprot/CRCM1_HUMAN CRCM1_HUMAN]] Combined immunodeficiency due to ORAI1 deficiency. The disease is caused by mutations affecting the gene represented in this entry. | ||
| - | + | == Function == | |
| - | ==Function== | + | |
[[http://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> [[http://www.uniprot.org/uniprot/CRCM1_HUMAN CRCM1_HUMAN]] Ca(2+) release-activated Ca(2+) (CRAC) channel subunit which mediates Ca(2+) influx following depletion of intracellular Ca(2+) stores and channel activation by the Ca(2+) sensor, STIM1. CRAC channels are the main pathway for Ca(2+) influx in T-cells and promote the immune response to pathogens by activating the transcription factor NFAT.<ref>PMID:16766533</ref> <ref>PMID:16807233</ref> <ref>PMID:16733527</ref> <ref>PMID:16645049</ref> <ref>PMID:16582901</ref> | [[http://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> [[http://www.uniprot.org/uniprot/CRCM1_HUMAN CRCM1_HUMAN]] Ca(2+) release-activated Ca(2+) (CRAC) channel subunit which mediates Ca(2+) influx following depletion of intracellular Ca(2+) stores and channel activation by the Ca(2+) sensor, STIM1. CRAC channels are the main pathway for Ca(2+) influx in T-cells and promote the immune response to pathogens by activating the transcription factor NFAT.<ref>PMID:16766533</ref> <ref>PMID:16807233</ref> <ref>PMID:16733527</ref> <ref>PMID:16645049</ref> <ref>PMID:16582901</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Orai1 calcium channels in the plasma membrane are activated by stromal interaction molecule-1 (STIM1), an endoplasmic reticulum calcium sensor, to mediate store-operated calcium entry (SOCE). The cytosolic region of STIM1 contains a long putative coiled-coil (CC)1 segment and shorter CC2 and CC3 domains. Here we present solution nuclear magnetic resonance structures of a trypsin-resistant CC1-CC2 fragment in the apo and Orai1-bound states. Each CC1-CC2 subunit forms a U-shaped structure that homodimerizes through antiparallel interactions between equivalent alpha-helices. The CC2:CC2' helix pair clamps two identical acidic Orai1 C-terminal helices at opposite ends of a hydrophobic/basic STIM-Orai association pocket. STIM1 mutants disrupting CC1:CC1' interactions attenuate, while variants promoting CC1 stability spontaneously activate Orai1 currents. CC2 mutations cause remarkable variability in Orai1 activation because of a dual function in binding Orai1 and autoinhibiting STIM1 oligomerization via interactions with CC3. We conclude that SOCE is activated through dynamic interplay between STIM1 and Orai1 helices. | ||
| - | + | STIM1/Orai1 coiled-coil interplay in the regulation of store-operated calcium entry.,Stathopulos PB, Schindl R, Fahrner M, Zheng L, Gasmi-Seabrook GM, Muik M, Romanin C, Ikura M Nat Commun. 2013 Dec 19;4:2963. doi: 10.1038/ncomms3963. PMID:24351972<ref>PMID:24351972</ref> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| - | [[Category: Ikura, M | + | == References == |
| - | [[Category: Stathopulos, P B | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Human]] | ||
| + | [[Category: Ikura, M]] | ||
| + | [[Category: Stathopulos, P B]] | ||
[[Category: Coiled-coil]] | [[Category: Coiled-coil]] | ||
[[Category: Orai1]] | [[Category: Orai1]] | ||
Revision as of 09:04, 15 February 2015
Solution structure of the STIM1 CC1-CC2 homodimer in complex with two Orai1 C-terminal domains.
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