5xa0: Difference between revisions
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==Crystal structure of inositol 1,4,5-trisphosphate receptor cytosolic domain== | |||
<StructureSection load='5xa0' size='340' side='right'caption='[[5xa0]], [[Resolution|resolution]] 5.81Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5xa0]] 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=5XA0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XA0 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 5.812Å</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=5xa0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xa0 OCA], [https://pdbe.org/5xa0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xa0 RCSB], [https://www.ebi.ac.uk/pdbsum/5xa0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xa0 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5xa0" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Inositol 1%2C4%2C5-Trisphosphate Receptor|Inositol 1%2C4%2C5-Trisphosphate Receptor]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Hamada K]] | |||
[[Category: Mikoshiba K]] | |||
[[Category: Miyatake H]] | |||
[[Category: Terauchi A]] | |||
Latest revision as of 10:57, 22 November 2023
Crystal structure of inositol 1,4,5-trisphosphate receptor cytosolic domainCrystal structure of inositol 1,4,5-trisphosphate receptor cytosolic domain
Structural highlights
FunctionITPR1_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 PubMedThe 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 AlsoReferences
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