ArticleNature2010
The amino-terminal disease hotspot of ryanodine receptors forms a cytoplasmic vestibule.
Article in Nature, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
109 citing papers in PubMed, 207 citations in OpenAlex.
- Structural basis for rosuvastatin-induced activation of skeletal muscle ryanodine receptor 1.Nature communications · 2026Article
- Structural basis for simvastatin-induced skeletal muscle weakness associated with type 1 ryanodine receptor T4709M mutation.The Journal of clinical investigation · 2025Article
- Catecholaminergic polymorphic ventricular tachycardia: A narrative review of recent advances in genetics, mechanisms, diagnosis, and treatment.Asian heart journal · 2025Review
- Advances in malignant hyperthermia: novel insights into heat-induced CaJournal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi · 2025Review
- Cryo-EM investigation of ryanodine receptor type 3.Nature communications · 2024Article
- Structural insights into the regulation of RyR1 by S100A1.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Disparate molecular mechanisms in cardiac ryanodine receptor channelopathies.Frontiers in molecular biosciences · 2024Article
- Cysteines 1078 and 2991 cross-linking plays a critical role in redox regulation of cardiac ryanodine receptor (RyR).Nature communications · 2023Article
- Cryo-EM analysis of scorpion toxin binding to Ryanodine Receptors reveals subconductance that is abolished by PKA phosphorylation.Science advances · 2023Article
- Editorial: The role of calcium and calcium binding proteins in cell physiology and disease.Frontiers in physiology · 2023Article
- Mice with R2509C-RYR1 mutation exhibit dysfunctional Ca2+ dynamics in primary skeletal myocytes.The Journal of general physiology · 2022Article
- Mutations in proteins involved in E-C coupling and SOCE and congenital myopathies.The Journal of general physiology · 2022Review
- Heat-hypersensitive mutants of ryanodine receptor type 1 revealed by microscopic heating.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- High-resolution structure of the membrane-embedded skeletal muscle ryanodine receptor.Structure (London, England : 1993) · 2022Article
- Correlation of Phenotype-Genotype and Protein Structure inFrontiers in neurology · 2022Article
- How Functional Genomics Can Keep Pace With VUS Identification.Frontiers in cardiovascular medicine · 2022Review
- Defective ryanodine receptor N-terminus inter-subunit interaction is a common mechanism in neuromuscular and cardiac disorders.Frontiers in physiology · 2022Article
- Structural Insight Into Ryanodine Receptor Channelopathies.Frontiers in pharmacology · 2022Review
- RyR1-related myopathy mutations in ATP and calcium binding sites impair channel regulation.Acta neuropathologica communications · 2021Article
- A Comparative Perspective on Functionally-Related, Intracellular Calcium Channels: The Insect Ryanodine and Inositol 1,4,5-Trisphosphate Receptors.Biomolecules · 2021Review
49 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Many physiological events require transient increases in cytosolic Ca(2+) concentrations. Ryanodine receptors (RyRs) are ion channels that govern the release of Ca(2+) from the endoplasmic and sarcoplasmic reticulum. Mutations in RyRs can lead to severe genetic conditions that affect both cardiac and skeletal muscle, but locating the mutated residues in the full-length channel structure has been difficult. Here we show the 2.5 Å resolution crystal structure of a region spanning three domains of RyR type 1 (RyR1), encompassing amino acid residues 1-559. The domains interact with each other through a predominantly hydrophilic interface. Docking in RyR1 electron microscopy maps unambiguously places the domains in the cytoplasmic portion of the channel, forming a 240-kDa cytoplasmic vestibule around the four-fold symmetry axis. We pinpoint the exact locations of more than 50 disease-associated mutations in full-length RyR1 and RyR2. The mutations can be classified into three groups: those that destabilize the interfaces between the three amino-terminal domains, disturb the folding of individual domains or affect one of six interfaces with other parts of the receptor. We propose a model whereby the opening of a RyR coincides with allosterically coupled motions within the N-terminal domains. This process can be affected by mutations that target various interfaces within and across subunits. The crystal structure provides a framework to understand the many disease-associated mutations in RyRs that have been studied using functional methods, and will be useful for developing new strategies to modulate RyR function in disease states.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.