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==Rabbit RyR1 with AMP-PCP and high Ca2+ embedded in nanodisc in inactivated conformation (Dataset-A)==
==Rabbit RyR1 with AMP-PCP and high Ca2+ embedded in nanodisc in inactivated conformation (Dataset-A)==
<StructureSection load='7tdg' size='340' side='right'caption='[[7tdg]]' scene=''>
<StructureSection load='7tdg' size='340' side='right'caption='[[7tdg]], [[Resolution|resolution]] 3.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TDG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TDG FirstGlance]. <br>
<table><tr><td colspan='2'>[[7tdg]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TDG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TDG FirstGlance]. <br>
</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=7tdg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tdg OCA], [https://pdbe.org/7tdg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tdg RCSB], [https://www.ebi.ac.uk/pdbsum/7tdg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tdg ProSAT]</span></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7tdj|7tdj]], [[7k0n|7k0n]], [[7tdk|7tdk]], [[7tdh|7tdh]], [[7k0t|7k0t]]</div></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=7tdg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tdg OCA], [https://pdbe.org/7tdg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tdg RCSB], [https://www.ebi.ac.uk/pdbsum/7tdg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tdg ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/RYR1_RABIT RYR1_RABIT]] Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules. Repeated very high-level exercise increases the open probability of the channel and leads to Ca(2+) leaking into the cytoplasm. Can also mediate the release of Ca(2+) from intracellular stores in neurons, and may thereby promote prolonged Ca(2+) signaling in the brain. Required for normal embryonic development of muscle fibers and skeletal muscle. Required for normal heart morphogenesis, skin development and ossification during embryogenesis (By similarity).<ref>PMID:10388749</ref> <ref>PMID:22036948</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Activation of the intracellular Ca(2+) channel ryanodine receptor (RyR) triggers a cytosolic Ca(2+) surge, while elevated cytosolic Ca(2+) inhibits the channel in a negative feedback mechanism. Cryo-EM of rabbit RyR1 embedded in nanodiscs under partially inactivating Ca(2+) conditions revealed an open and a closed-inactivated conformation. Ca(2+) binding to the high affinity site engages the central and C-terminal domains into a block, which pries the S6 four-helix bundle open. Further rotation of this block pushes S6 toward the central axis, closing (inactivating) the channel. Main characteristics of the Ca(2+)-inactivated conformation are downward conformation of the cytoplasmic assembly and tightly-knit subunit interface contributed by a fully occupied Ca(2+) activation site, two inter-subunit resolved lipids, and two salt bridges between the EF hand domain and the S2-S3 loop validated by disease-causing mutations. The structural insight illustrates the prior Ca(2+) activation prerequisite for Ca(2+) inactivation and provides for seamless transition from inactivated to closed conformations.
Ca(2+)-inactivation of the mammalian ryanodine receptor type 1 in a lipidic environment revealed by cryo-EM.,Nayak AR, Samso M Elife. 2022 Mar 8;11. pii: 75568. doi: 10.7554/eLife.75568. PMID:35257661<ref>PMID:35257661</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7tdg" style="background-color:#fffaf0;"></div>
==See Also==
*[[Ryanodine receptor 3D structures|Ryanodine receptor 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Nayak AR]]
[[Category: Oryctolagus cuniculus]]
[[Category: Samso M]]
[[Category: Nayak, A R]]
[[Category: Samso, M]]
[[Category: Ca2+]]
[[Category: Excitation-contraction coupling]]
[[Category: Inactivation]]
[[Category: Intracellular calcium channel]]
[[Category: Ryanodine receptor]]
[[Category: Ryr1]]
[[Category: Transport protein]]

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