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==Crystal structure of inositol 1,4,5-trisphosphate receptor large cytosolic domain with inositol 1,4,5-trisphosphate==
==Crystal structure of inositol 1,4,5-trisphosphate receptor large cytosolic domain with inositol 1,4,5-trisphosphate==
<StructureSection load='5gug' size='340' side='right' caption='[[5gug]], [[Resolution|resolution]] 7.40&Aring;' scene=''>
<StructureSection load='5gug' size='340' side='right'caption='[[5gug]], [[Resolution|resolution]] 7.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5gug]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GUG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GUG FirstGlance]. <br>
<table><tr><td colspan='2'>[[5gug]] 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=5GUG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GUG FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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]] 7.399&#8491;</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=5gug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gug OCA], [http://pdbe.org/5gug PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gug RCSB], [http://www.ebi.ac.uk/pdbsum/5gug PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gug ProSAT]</span></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5gug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gug OCA], [https://pdbe.org/5gug PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5gug RCSB], [https://www.ebi.ac.uk/pdbsum/5gug PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5gug 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;">
== 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<ref>PMID:28416699</ref>
==See Also==
 
*[[Inositol 1%2C4%2C5-Trisphosphate Receptor|Inositol 1%2C4%2C5-Trisphosphate Receptor]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5gug" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Hamada, K]]
[[Category: Large Structures]]
[[Category: Mikoshiba, K]]
[[Category: Mus musculus]]
[[Category: Miyatake, H]]
[[Category: Hamada K]]
[[Category: Terauchi, A]]
[[Category: Mikoshiba K]]
[[Category: Metal transport]]
[[Category: Miyatake H]]
[[Category: Receptor channel calcium]]
[[Category: Terauchi A]]

Latest revision as of 12:13, 20 March 2024

Crystal structure of inositol 1,4,5-trisphosphate receptor large cytosolic domain with inositol 1,4,5-trisphosphateCrystal structure of inositol 1,4,5-trisphosphate receptor large cytosolic domain with inositol 1,4,5-trisphosphate

Structural highlights

5gug is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 7.399Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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

5gug, resolution 7.40Å

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