ArticleThe Journal of biological chemistry2013
Structural determinants of skeletal muscle ryanodine receptor gating.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Pharmacogenomic profile of actionable molecular variants related to drugs commonly used in anesthesia: WES analysis reveals new mutations.Frontiers in pharmacology · 2023Article
- Molecular Dynamics Simulations of the Cardiac Ryanodine Receptor Type 2 (RyR2) Gating Mechanism.The journal of physical chemistry. B · 2022Article
- Mapping co-regulatory interactions among ligand-binding sites in ryanodine receptor 1.Proteins · 2022Article
- Experimentally-driven protein structure modeling.Journal of proteomics · 2020Review
- CaThe Journal of biological chemistry · 2018Article
- G4941K substitution in the pore-lining S6 helix of the skeletal muscle ryanodine receptor increases RyR1 sensitivity to cytosolic and luminal CaThe Journal of biological chemistry · 2018Article
- Malignant Hyperthermia in the Post-Genomics Era: New Perspectives on an Old Concept.Anesthesiology · 2018Review
- The structural basis of ryanodine receptor ion channel function.The Journal of general physiology · 2017Review
- Congenital myopathies: clinical phenotypes and new diagnostic tools.Italian journal of pediatrics · 2017Review
- Extensive Ca2+ leak through K4750Q cardiac ryanodine receptors caused by cytosolic and luminal Ca2+ hypersensitivity.The Journal of general physiology · 2017Article
- A guide to the 3D structure of the ryanodine receptor type 1 by cryoEM.Protein science : a publication of the Protein Society · 2017Review
- Unambiguous observation of blocked states reveals altered, blocker-induced, cardiac ryanodine receptor gating.Scientific reports · 2016Article
- Structural insights into Ca(2+)-activated long-range allosteric channel gating of RyR1.Cell research · 2016Article
- Structures of the colossal RyR1 calcium release channel.Current opinion in structural biology · 2016Review
- Interaction of ions with the luminal sides of wild-type and mutated skeletal muscle ryanodine receptors.Journal of molecular modeling · 2016Article
- Channel Gating Dependence on Pore Lining Helix Glycine Residues in Skeletal Muscle Ryanodine Receptor.The Journal of biological chemistry · 2015Article
- Arrhythmogenesis in a catecholaminergic polymorphic ventricular tachycardia mutation that depresses ryanodine receptor function.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- A new cytoplasmic interaction between junctin and ryanodine receptor Ca2+ release channels.Journal of cell science · 2015Article
- Single-particle cryo-EM of the ryanodine receptor channel in an aqueous environment.European journal of translational myology · 2015Article
- Selecting ions by size in a calcium channel: the ryanodine receptor case study.Biophysical journal · 2014Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Ryanodine receptor type 1 (RyR1) releases Ca(2+) from intracellular stores upon nerve impulse to trigger skeletal muscle contraction. Effector binding at the cytoplasmic domain tightly controls gating of the pore domain of RyR1 to release Ca(2+). However, the molecular mechanism that links effector binding to channel gating is unknown due to lack of structural data. Here, we used a combination of computational and electrophysiological methods and cryo-EM densities to generate structural models of the open and closed states of RyR1. Using our structural models, we identified an interface between the pore-lining helix (Tyr-4912-Glu-4948) and a linker helix (Val-4830-Val-4841) that lies parallel to the cytoplasmic membrane leaflet. To test the hypothesis that this interface controls RyR1 gating, we designed mutations in the linker helix to stabilize either the open (V4830W and T4840W) or closed (H4832W and G4834W) state and validated them using single channel experiments. To further confirm this interface, we designed mutations in the pore-lining helix to stabilize the closed state (Q4947N, Q4947T, and Q4947S), which we also validated using single channel experiments. The channel conductance and selectivity of the mutations that we designed in the linker and pore-lining helices were indistinguishable from those of WT RyR1, demonstrating our ability to modulate RyR1 gating without affecting ion permeation. Our integrated computational and experimental approach significantly advances the understanding of the structure and function of an unusually large ion channel.
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