View source for 8eaq


==Structure of the full-length IP3R1 channel determined at high Ca2+==
<StructureSection load='8eaq' size='340' side='right'caption='[[8eaq]], [[Resolution|resolution]] 3.26&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8eaq]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8EAQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EAQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.26&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PLX:(9R,11S)-9-({[(1S)-1-HYDROXYHEXADECYL]OXY}METHYL)-2,2-DIMETHYL-5,7,10-TRIOXA-2LAMBDA~5~-AZA-6LAMBDA~5~-PHOSPHAOCTACOSANE-6,6,11-TRIOL'>PLX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8eaq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8eaq OCA], [https://pdbe.org/8eaq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8eaq RCSB], [https://www.ebi.ac.uk/pdbsum/8eaq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8eaq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ITPR1_RAT ITPR1_RAT] 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 (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Inositol-1,4,5-trisphosphate receptors (IP(3)Rs) are activated by IP(3) and Ca(2+) and their gating is regulated by various intracellular messengers that finely tune the channel activity. Here, using single particle cryo-EM analysis we determined 3D structures of the nanodisc-reconstituted IP(3)R1 channel in two ligand-bound states. These structures provide unprecedented details governing binding of IP(3), Ca(2+) and ATP, revealing conformational changes that couple ligand-binding to channel opening. Using a deep-learning approach and 3D variability analysis we extracted molecular motions of the key protein domains from cryo-EM density data. We find that IP(3) binding relies upon intrinsic flexibility of the ARM2 domain in the tetrameric channel. Our results highlight a key role of dynamic side chains in regulating gating behavior of IP(3)R channels. This work represents a stepping-stone to developing mechanistic understanding of conformational pathways underlying ligand-binding, activation and regulation of the channel.

Conformational motions and ligand-binding underlying gating and regulation in IP(3)R channel.,Fan G, Baker MR, Terry LE, Arige V, Chen M, Seryshev AB, Baker ML, Ludtke SJ, Yule DI, Serysheva II Nat Commun. 2022 Nov 14;13(1):6942. doi: 10.1038/s41467-022-34574-1. PMID:36376291<ref>PMID:36376291</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8eaq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Arige V]]
[[Category: Baker ML]]
[[Category: Baker MR]]
[[Category: Chen M]]
[[Category: Fan G]]
[[Category: Ludtke SJ]]
[[Category: Seryshev AB]]
[[Category: Serysheva II]]
[[Category: Terry LE]]
[[Category: Yule DI]]