+Open data
-Basic information
Entry | Database: PDB / ID: 8sen | |||||||||
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Title | Cryo-EM Structure of RyR1 | |||||||||
Components |
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Keywords | TRANSPORT PROTEIN / Calcium ion channel / skeletal muscle / nucleotide / homotetramer | |||||||||
Function / homology | Function and homology information ATP-gated ion channel activity / positive regulation of sequestering of calcium ion / cyclic nucleotide binding / negative regulation of calcium-mediated signaling / negative regulation of insulin secretion involved in cellular response to glucose stimulus / terminal cisterna / negative regulation of release of sequestered calcium ion into cytosol / ryanodine receptor complex / ryanodine-sensitive calcium-release channel activity / neuronal action potential propagation ...ATP-gated ion channel activity / positive regulation of sequestering of calcium ion / cyclic nucleotide binding / negative regulation of calcium-mediated signaling / negative regulation of insulin secretion involved in cellular response to glucose stimulus / terminal cisterna / negative regulation of release of sequestered calcium ion into cytosol / ryanodine receptor complex / ryanodine-sensitive calcium-release channel activity / neuronal action potential propagation / insulin secretion involved in cellular response to glucose stimulus / release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / ossification involved in bone maturation / response to redox state / protein maturation by protein folding / 'de novo' protein folding / skin development / negative regulation of heart rate / FK506 binding / organelle membrane / positive regulation of axon regeneration / cellular response to caffeine / channel regulator activity / outflow tract morphogenesis / intracellularly gated calcium channel activity / glutathione transferase / glutathione transferase activity / smooth muscle contraction / response to vitamin E / toxic substance binding / voltage-gated calcium channel activity / smooth endoplasmic reticulum / calcium channel inhibitor activity / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / skeletal muscle fiber development / T cell proliferation / striated muscle contraction / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / Ion homeostasis / muscle contraction / release of sequestered calcium ion into cytosol / regulation of cytosolic calcium ion concentration / sarcoplasmic reticulum membrane / calcium channel complex / glutathione metabolic process / cellular response to calcium ion / sarcoplasmic reticulum / peptidylprolyl isomerase / peptidyl-prolyl cis-trans isomerase activity / calcium ion transmembrane transport / calcium-mediated signaling / response to hydrogen peroxide / calcium channel activity / Stimuli-sensing channels / sarcolemma / Z disc / intracellular calcium ion homeostasis / disordered domain specific binding / positive regulation of cytosolic calcium ion concentration / protein refolding / protein homotetramerization / transmembrane transporter binding / calmodulin binding / signaling receptor binding / calcium ion binding / ATP binding / identical protein binding / membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) Oryctolagus cuniculus (rabbit) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.49 Å | |||||||||
Authors | Cholak, S. / Saville, J.W. / Zhu, X. / Berezuk, A.M. / Tuttle, K.S. / Haji-Ghassemi, O. / Van Petegem, F. / Subramaniam, S. | |||||||||
Funding support | Canada, 2items
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Citation | Journal: Structure / Year: 2023 Title: Allosteric modulation of ryanodine receptor RyR1 by nucleotide derivatives. Authors: Spencer Cholak / James W Saville / Xing Zhu / Alison M Berezuk / Katharine S Tuttle / Omid Haji-Ghassemi / Francisco J Alvarado / Filip Van Petegem / Sriram Subramaniam / Abstract: The coordinated release of Ca from the sarcoplasmic reticulum (SR) is critical for excitation-contraction coupling. This release is facilitated by ryanodine receptors (RyRs) that are embedded in the ...The coordinated release of Ca 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). To obtain structural insights into the mechanism of RyR1 priming by ATP, we determined several cryo-EM structures of RyR1 bound individually to ATP-γ-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 (>170 Å) 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. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8sen.cif.gz | 4.2 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8sen.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8sen.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8sen_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
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Full document | 8sen_full_validation.pdf.gz | 1.7 MB | Display | |
Data in XML | 8sen_validation.xml.gz | 416.3 KB | Display | |
Data in CIF | 8sen_validation.cif.gz | 649.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/se/8sen ftp://data.pdbj.org/pub/pdb/validation_reports/se/8sen | HTTPS FTP |
-Related structure data
Related structure data | 40422MC 8seoC 8sepC 8seqC 8serC 8sesC 8setC 8seuC 8sevC 8sewC 8sexC 8seyC 8sezC 8sf0C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
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