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Entry | Database: PDB / ID: 8set | |||||||||
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Title | Cryo-EM Structure of RyR1 + cAMP | |||||||||
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 insulin secretion involved in cellular response to glucose stimulus / terminal cisterna / ryanodine receptor complex / negative regulation of release of sequestered calcium ion into cytosol / ryanodine-sensitive calcium-release channel activity / neuronal action potential propagation / insulin secretion involved in cellular response to glucose stimulus ...ATP-gated ion channel activity / positive regulation of sequestering of calcium ion / cyclic nucleotide binding / negative regulation of insulin secretion involved in cellular response to glucose stimulus / terminal cisterna / ryanodine receptor complex / negative regulation of release of sequestered calcium ion into cytosol / 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 / cell communication by electrical coupling involved in cardiac conduction / response to redox state / protein maturation by protein folding / 'de novo' protein folding / skin development / negative regulation of heart rate / negative regulation of phosphoprotein phosphatase activity / FK506 binding / positive regulation of axon regeneration / cellular response to caffeine / outflow tract morphogenesis / intracellularly gated calcium channel activity / organelle membrane / glutathione transferase / : / glutathione transferase activity / smooth muscle contraction / toxic substance binding / smooth endoplasmic reticulum / negative regulation of ryanodine-sensitive calcium-release channel activity / response to vitamin E / voltage-gated calcium channel activity / calcium channel inhibitor activity / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / skeletal muscle fiber development / protein peptidyl-prolyl isomerization / striated muscle contraction / T cell proliferation / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / release of sequestered calcium ion into cytosol / Ion homeostasis / regulation of ryanodine-sensitive calcium-release channel activity / sarcoplasmic reticulum membrane / calcium channel complex / muscle contraction / regulation of cytosolic calcium ion concentration / cellular response to calcium ion / glutathione metabolic process / sarcoplasmic reticulum / peptidylprolyl isomerase / peptidyl-prolyl cis-trans isomerase activity / calcium ion transmembrane transport / calcium channel activity / response to hydrogen peroxide / 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 / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) Oryctolagus cuniculus (rabbit) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.42 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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PDBx/mmCIF format | 8set.cif.gz | 4.2 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8set.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8set.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8set_validation.pdf.gz | 1.7 MB | Display | wwPDB validaton report |
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Full document | 8set_full_validation.pdf.gz | 1.9 MB | Display | |
Data in XML | 8set_validation.xml.gz | 420.5 KB | Display | |
Data in CIF | 8set_validation.cif.gz | 656 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/se/8set ftp://data.pdbj.org/pub/pdb/validation_reports/se/8set | HTTPS FTP |
-Related structure data
Related structure data | 40428MC 8senC 8seoC 8sepC 8seqC 8serC 8sesC 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 |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
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