View source for 8sew


==Cryo-EM Structure of RyR1 + ADP (Local Refinement of TMD)==
<StructureSection load='8sew' size='340' side='right'caption='[[8sew]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8sew]] 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=8SEW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SEW 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]] 2.89&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</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=8sew FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8sew OCA], [https://pdbe.org/8sew PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8sew RCSB], [https://www.ebi.ac.uk/pdbsum/8sew PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8sew ProSAT]</span></td></tr>
</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 ==
The coordinated release of Ca(2+) from the sarcoplasmic reticulum (SR) is critical for excitation-contraction coupling. This release is facilitated by ryanodine receptors (RyRs) that are embedded in the SR membrane. In skeletal muscle, activity of RyR1 is regulated by metabolites such as ATP, which upon binding increase channel open probability (P(o)). To obtain structural insights into the mechanism of RyR1 priming by ATP, we determined several cryo-EM structures of RyR1 bound individually to ATP-gamma-S, ADP, AMP, adenosine, adenine, and cAMP. We demonstrate that adenine and adenosine bind RyR1, but AMP is the smallest ATP derivative capable of inducing long-range (&gt;170 A) structural rearrangements associated with channel activation, establishing a structural basis for key binding site interactions that are the threshold for triggering quaternary structural changes. Our finding that cAMP also induces these structural changes and results in increased channel opening suggests its potential role as an endogenous modulator of RyR1 conductance.

Allosteric modulation of ryanodine receptor RyR1 by nucleotide derivatives.,Cholak S, Saville JW, Zhu X, Berezuk AM, Tuttle KS, Haji-Ghassemi O, Alvarado FJ, Van Petegem F, Subramaniam S Structure. 2023 Jul 6;31(7):790-800.e4. doi: 10.1016/j.str.2023.04.009. Epub 2023 , May 15. PMID:37192614<ref>PMID:37192614</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8sew" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ryanodine receptor 3D structures|Ryanodine receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Oryctolagus cuniculus]]
[[Category: Berezuk AM]]
[[Category: Cholak S]]
[[Category: Haji-Ghassemi O]]
[[Category: Saville JW]]
[[Category: Subramaniam S]]
[[Category: Tuttle KS]]
[[Category: Van Petegem F]]
[[Category: Zhu X]]