8ear: Difference between revisions

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'''Unreleased structure'''


The entry 8ear is ON HOLD
==Structure of the full-length IP3R1 channel determined in the presence of Calcium/IP3/ATP==
<StructureSection load='8ear' size='340' side='right'caption='[[8ear]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ear]] 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=8EAR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EAR 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]] 3.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=I3P:D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE'>I3P</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=8ear FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ear OCA], [https://pdbe.org/8ear PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ear RCSB], [https://www.ebi.ac.uk/pdbsum/8ear PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ear 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.


Authors: Fan, G., Baker, M.R., Terry, L.E., Arige, V., Chen, M., Seryshev, A.B., Baker, M.L., Ludtke, S.J., Yule, D.I., Serysheva, I.I.
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>


Description: Structure of the full-length IP3R1 channel determined in the presence of Calcium/IP3/ATP
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Chen, M]]
<div class="pdbe-citations 8ear" style="background-color:#fffaf0;"></div>
[[Category: Terry, L.E]]
== References ==
[[Category: Seryshev, A.B]]
<references/>
[[Category: Baker, M.R]]
__TOC__
[[Category: Serysheva, I.I]]
</StructureSection>
[[Category: Ludtke, S.J]]
[[Category: Large Structures]]
[[Category: Yule, D.I]]
[[Category: Rattus norvegicus]]
[[Category: Baker, M.L]]
[[Category: Arige V]]
[[Category: Arige, V]]
[[Category: Baker ML]]
[[Category: Fan, G]]
[[Category: Baker MR]]
[[Category: Chen M]]
[[Category: Fan G]]
[[Category: Ludtke SJ]]
[[Category: Seryshev AB]]
[[Category: Serysheva II]]
[[Category: Terry LE]]
[[Category: Yule DI]]

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