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| | <StructureSection load='5xa1' size='340' side='right'caption='[[5xa1]], [[Resolution|resolution]] 6.20Å' scene=''> | | <StructureSection load='5xa1' size='340' side='right'caption='[[5xa1]], [[Resolution|resolution]] 6.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5xa1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XA1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5XA1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5xa1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XA1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XA1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I3P:D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE'>I3P</scene></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]] 6.204Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5x9z|5x9z]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I3P:D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE'>I3P</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Itpr1, Insp3r, Pcd6, Pcp1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=5xa1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xa1 OCA], [https://pdbe.org/5xa1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xa1 RCSB], [https://www.ebi.ac.uk/pdbsum/5xa1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xa1 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5xa1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xa1 OCA], [http://pdbe.org/5xa1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xa1 RCSB], [http://www.ebi.ac.uk/pdbsum/5xa1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xa1 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ITPR1_MOUSE ITPR1_MOUSE]] Intracellular channel that mediates calcium release from the endoplasmic reticulum following stimulation by inositol 1,4,5-trisphosphate. Plays a role in ER stress-induced apoptosis. Cytoplasmic calcium released from the ER triggers apoptosis by the activation of CaM kinase II, eventually leading to the activation of downstream apoptosis pathways.<ref>PMID:2554142</ref> <ref>PMID:19752026</ref> <ref>PMID:20813840</ref> | + | [https://www.uniprot.org/uniprot/ITPR1_MOUSE ITPR1_MOUSE] Intracellular channel that mediates calcium release from the endoplasmic reticulum following stimulation by inositol 1,4,5-trisphosphate. Plays a role in ER stress-induced apoptosis. Cytoplasmic calcium released from the ER triggers apoptosis by the activation of CaM kinase II, eventually leading to the activation of downstream apoptosis pathways.<ref>PMID:2554142</ref> <ref>PMID:19752026</ref> <ref>PMID:20813840</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Hamada, K]] | + | [[Category: Hamada K]] |
| - | [[Category: Mikoshiba, K]] | + | [[Category: Mikoshiba K]] |
| - | [[Category: Miyatake, H]] | + | [[Category: Miyatake H]] |
| - | [[Category: Terauchi, A]] | + | [[Category: Terauchi A]] |
| - | [[Category: Metal transport]]
| + | |
| - | [[Category: Receptor channel calcium]]
| + | |
| Structural highlights
Function
ITPR1_MOUSE Intracellular channel that mediates calcium release from the endoplasmic reticulum following stimulation by inositol 1,4,5-trisphosphate. Plays a role in ER stress-induced apoptosis. Cytoplasmic calcium released from the ER triggers apoptosis by the activation of CaM kinase II, eventually leading to the activation of downstream apoptosis pathways.[1] [2] [3]
Publication Abstract from PubMed
The inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) is an IP3-gated ion channel that releases calcium ions (Ca2+) from the endoplasmic reticulum. The IP3-binding sites in the large cytosolic domain are distant from the Ca2+ conducting pore, and the allosteric mechanism of how IP3 opens the Ca2+ channel remains elusive. Here, we identify a long-range gating mechanism uncovered by channel mutagenesis and X-ray crystallography of the large cytosolic domain of mouse type 1 IP3R in the absence and presence of IP3 Analyses of two distinct space group crystals uncovered an IP3-dependent global translocation of the curvature alpha-helical domain interfacing with the cytosolic and channel domains. Mutagenesis of the IP3R channel revealed an essential role of a leaflet structure in the alpha-helical domain. These results suggest that the curvature alpha-helical domain relays IP3-controlled global conformational dynamics to the channel through the leaflet, conferring long-range allosteric coupling from IP3 binding to the Ca2+ channel.
IP3-mediated gating mechanism of the IP3 receptor revealed by mutagenesis and X-ray crystallography.,Hamada K, Miyatake H, Terauchi A, Mikoshiba K Proc Natl Acad Sci U S A. 2017 May 2;114(18):4661-4666. doi:, 10.1073/pnas.1701420114. Epub 2017 Apr 17. PMID:28416699[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Furuichi T, Yoshikawa S, Miyawaki A, Wada K, Maeda N, Mikoshiba K. Primary structure and functional expression of the inositol 1,4,5-trisphosphate-binding protein P400. Nature. 1989 Nov 2;342(6245):32-8. PMID:2554142 doi:http://dx.doi.org/10.1038/342032a0
- ↑ Li G, Mongillo M, Chin KT, Harding H, Ron D, Marks AR, Tabas I. Role of ERO1-alpha-mediated stimulation of inositol 1,4,5-triphosphate receptor activity in endoplasmic reticulum stress-induced apoptosis. J Cell Biol. 2009 Sep 21;186(6):783-92. doi: 10.1083/jcb.200904060. Epub 2009 Sep, 14. PMID:19752026 doi:http://dx.doi.org/10.1083/jcb.200904060
- ↑ Yamazaki H, Chan J, Ikura M, Michikawa T, Mikoshiba K. Tyr-167/Trp-168 in type 1/3 inositol 1,4,5-trisphosphate receptor mediates functional coupling between ligand binding and channel opening. J Biol Chem. 2010 Nov 12;285(46):36081-91. doi: 10.1074/jbc.M110.140129. Epub, 2010 Sep 2. PMID:20813840 doi:http://dx.doi.org/10.1074/jbc.M110.140129
- ↑ Hamada K, Miyatake H, Terauchi A, Mikoshiba K. IP3-mediated gating mechanism of the IP3 receptor revealed by mutagenesis and X-ray crystallography. Proc Natl Acad Sci U S A. 2017 May 2;114(18):4661-4666. doi:, 10.1073/pnas.1701420114. Epub 2017 Apr 17. PMID:28416699 doi:http://dx.doi.org/10.1073/pnas.1701420114
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