ArticleProceedings of the National Academy of Sciences of the United States of America2013
Unstructured to structured transition of an intrinsically disordered protein peptide in coupling Ca²⁺-sensing and SK channel activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed, 66 citations in OpenAlex.
- Structural mechanisms for inhibition and activation of human small-conductance CaNature communications · 2026Article
- Structural basis for the subtype-selectivity of KNature communications · 2026Article
- 6,7-Dichloro-1H-indole-2,3-dione-3-oxime functions as a superagonist for the intermediate-conductance CaMolecular pharmacology · 2025Article
- VTA dopamine neurons are hyperexcitable in 3xTg-AD mice due to casein kinase 2-dependent SK channel dysfunction.Nature communications · 2024Article
- Dysfunction of Small-Conductance CaCells · 2024Article
- Cilia and Extracellular Vesicles in Brain Development and Disease.Biological psychiatry · 2024Review
- Intrinsically disordered regions are poised to act as sensors of cellular chemistry.Trends in biochemical sciences · 2023Review
- VTA dopamine neurons are hyperexcitable in 3xTg-AD mice due to casein kinase 2-dependent SK channel dysfunction.bioRxiv : the preprint server for biology · 2023Article
- What Makes a Good Protein-Protein Interaction Stabilizer: Analysis and Application of the Dual-Binding Mechanism.ACS central science · 2023Article
- Article
- Multiubiquitination of TRPV4 reduces channel activity independent of surface localization.The Journal of biological chemistry · 2022Article
- Subtype-selective positive modulation of KBritish journal of pharmacology · 2022Article
- Differential modulation of SK channel subtypes by phosphorylation.Cell calcium · 2021Article
- Hydrophobic interactions between the HA helix and S4-S5 linker modulate apparent CaActa physiologica (Oxford, England) · 2021Article
- Physiology and Therapeutic Potential of SK, H, and M Medium AfterHyperPolarization Ion Channels.Frontiers in molecular neuroscience · 2021Review
- Atomistic Insights of Calmodulin Gating of Complete Ion Channels.International journal of molecular sciences · 2020Review
- Pharmacology of Small- and Intermediate-Conductance Calcium-Activated Potassium Channels.Annual review of pharmacology and toxicology · 2020Review
- A Pilot Study of All-Computational Drug Design Protocol-From Structure Prediction to Interaction Analysis.Frontiers in chemistry · 2020Article
- Calmodulin-Calcineurin Interaction beyond the Calmodulin-Binding Region Contributes to Calcineurin Activation.Biochemistry · 2019Article
- Critical regulation of atherosclerosis by the KCa3.1 channel and the retargeting of this therapeutic target in in-stent neoatherosclerosis.Journal of molecular medicine (Berlin, Germany) · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Most proteins, such as ion channels, form well-organized 3D structures to carry out their specific functions. A typical voltage-gated potassium channel subunit has six transmembrane segments (S1-S6) to form the voltage-sensing domain and the pore domain. Conformational changes of these domains result in opening of the channel pore. Intrinsically disordered (ID) proteins/peptides are considered equally important for the protein functions. However, it is difficult to explore the structural features underlying the functions of ID proteins/peptides by conventional methods, such as X-ray crystallography, because of the flexibility of their secondary structures. Unlike voltage-gated potassium channels, families of small- and intermediate-conductance Ca(2+)-activated potassium (SK/IK) channels with important roles in regulating membrane excitability are activated exclusively by Ca(2+)-bound calmodulin (CaM). Upon binding of Ca(2+) to CaM, a 2 × 2 structure forms between CaM and the CaM-binding domain. A channel fragment that connects S6 and the CaM-binding domain is not visible in the protein crystal structure, suggesting that this fragment is an ID fragment. Here we show that the conformation of the ID fragment in SK channels becomes readily identifiable in the presence of NS309, the most potent compound that potentiates the channel activities. This well-defined conformation of the ID fragment, stabilized by NS309, increases the channel open probability at a given Ca(2+) concentration. Our results demonstrate that the ID fragment, itself a target for drugs modulating SK channel activities, plays a unique role in coupling Ca(2+) sensing by CaM and mechanical opening of SK channels.
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.