ArticleThe Journal of biological chemistry2016
S100A1 Protein Does Not Compete with Calmodulin for Ryanodine Receptor Binding but Structurally Alters the Ryanodine Receptor·Calmodulin Complex.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Correlation of phenotype with genotype and protein structure in RYR1-related disorders.Journal of neurology · 2018Trial
- Structural and Functional Regulation of RyR2 in Cardiac Calcium Handling and Arrhythmogenesis.Biomedicines · 2026Review
- Structural insights into the regulation of RyR1 by S100A1.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- S100A1's single cysteine is an indispensable redox switch for the protection against diastolic calcium waves in cardiomyocytes.American journal of physiology. Heart and circulatory physiology · 2024Article
- Kinetics and mapping of Ca-driven calmodulin conformations on skeletal and cardiac muscle ryanodine receptors.Nature communications · 2024Article
- Isolated Cardiac Ryanodine Receptor Function Varies Between Mammals.The Journal of membrane biology · 2024Article
- Molecular Mechanism of a FRET Biosensor for the Cardiac Ryanodine Receptor Pathologically Leaky State.International journal of molecular sciences · 2023Article
- Molecular Mechanism of a FRET Biosensor for the Cardiac Ryanodine Receptor Pathologically Leaky State.bioRxiv : the preprint server for biology · 2023Article
- New N-aryl-N-alkyl-thiophene-2-carboxamide compound enhances intracellular CaBiophysical journal · 2023Article
- Synergistic FRET assays for drug discovery targeting RyR2 channels.Journal of molecular and cellular cardiology · 2022Article
- HAntioxidants (Basel, Switzerland) · 2022Review
- Structural Insight Into Ryanodine Receptor Channelopathies.Frontiers in pharmacology · 2022Review
- Article
- Met125 is essential for maintaining the structural integrity of calmodulin's C-terminal domain.Scientific reports · 2020Article
- The Arianna thread: the matching of S-100 family with the RyR's muscle receptor.European journal of translational myology · 2020Article
- Resolved Structural States of Calmodulin in Regulation of Skeletal Muscle Calcium Release.Biophysical journal · 2020Article
- Skeletal muscle: A review of molecular structure and function, in health and disease.Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
- The CaMKII inhibitor KN93-calmodulin interaction and implications for calmodulin tuning of NaCell calcium · 2019Article
- Unnatural verticilide enantiomer inhibits type 2 ryanodine receptor-mediated calcium leak and is antiarrhythmic.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Loss of S100A1 expression leads to CaPhysiological reports · 2018Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
S100A1 has been suggested as a therapeutic agent to enhance myocyte Ca(2+) cycling in heart failure, but its molecular mode of action is poorly understood. Using FRET, we tested the hypothesis that S100A1 directly competes with calmodulin (CaM) for binding to intact, functional ryanodine receptors type I (RyR1) and II (RyR2) from skeletal and cardiac muscle, respectively. Our FRET readout provides an index of acceptor-labeled CaM binding near donor-labeled FKBP (FK506-binding protein 12.6) on the cytoplasmic domain of RyR in isolated sarcoplasmic reticulum vesicles. S100A1 (0.01-400 μm) partially inhibited FRET (i.e. CaM binding), with Ki > 10 μm, for both RyR1 and RyR2. The high [S100A1] required for partial effects on FRET indicates a lack of competition by S100A1 on CaM/RyR binding under normal physiological conditions. High-resolution analysis of time-resolved FRET detects two structural states of RyR-bound CaM, which respond to [Ca(2+)] and are isoform-specific. The distribution of these structural states was perturbed only by high micromolar [S100A1], which promoted a shift of bound CaM to a lower FRET orientation (without altering the amount of CaM bound to RyR). Thus, high micromolar S100A1 does alter the CaM/RyR interaction, without involving competition. Nevertheless, submicromolar S100A1 can alter RyR function, an effect that is influenced by both [Ca(2+)] and [CaM]. We conclude that CaM and S100A1 can concurrently bind to and functionally modulate RyR1 and RyR2, but this does not involve direct competition at the RyR CaM binding site.
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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.