ArticleBiophysical journal2013
Building KCNQ1/KCNE1 channel models and probing their interactions by molecular-dynamics simulations.
Article in Biophysical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
32 citing papers in PubMed, 55 citations in OpenAlex.
- Functional Profiling ofCirculation. Genomic and precision medicine · 2025Article
- A physiologically-relevant intermediate state structure of a voltage-gated potassium channel.Nature communications · 2025Article
- Dynamic protein-protein interactions of KCNQ1 and KCNE1 measured by EPR line shape analysis.Biochimica et biophysica acta. Biomembranes · 2024Article
- Genetic characterization of KCNQ1 variants improves risk stratification in type 1 long QT syndrome patients.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2024Article
- The role of native cysteine residues in the oligomerization of KCNQ1 channels.Biochemical and biophysical research communications · 2023Article
- Modulation of the IBBA advances · 2023Article
- Purification and membrane interactions of human KCNQ1Biochimica et biophysica acta. Biomembranes · 2022Article
- Delayed KCNQ1/KCNE1 assembly on the cell surface helps IThe Journal of physiology · 2021Article
- Article
- Article
- The membrane protein KCNQ1 potassium ion channel: Functional diversity and current structural insights.Biochimica et biophysica acta. Biomembranes · 2020Review
- Two-stage electro-mechanical coupling of a KNature communications · 2020Article
- Physical and functional interaction sites in cytoplasmic domains of KCNQ1 and KCNE1 channel subunits.American journal of physiology. Heart and circulatory physiology · 2020Article
- Structure-function relationship of the slow delayed rectifier channel: impactful questions in 2020 and beyond.American journal of physiology. Heart and circulatory physiology · 2020Article
- Polyunsaturated Fatty Acids as Modulators of KFrontiers in physiology · 2020Review
- Structures Illuminate Cardiac Ion Channel Functions in Health and in Long QT Syndrome.Frontiers in pharmacology · 2020Review
- Article
- Effects of β-subunit on gating of a potassium ion channel: Molecular simulations of cardiac IKs activation.Journal of molecular and cellular cardiology · 2018Article
- KCNE1 tunes the sensitivity of KeLife · 2018Article
- Modeling the Hidden Pathways of IKs Channel Activation.Biophysical journal · 2018Article
Corrections and comments
- Commented on by
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The slow delayed rectifier (I(KS)) channel is composed of KCNQ1 (pore-forming) and KCNE1 (auxiliary) subunits, and functions as a repolarization reserve in the human heart. Design of I(KS)-targeting anti-arrhythmic drugs requires detailed three-dimensional structures of the KCNQ1/KCNE1 complex, a task made possible by Kv channel crystal structures (templates for KCNQ1 homology-modeling) and KCNE1 NMR structures. Our goal was to build KCNQ1/KCNE1 models and extract mechanistic information about their interactions by molecular-dynamics simulations in an explicit lipid/solvent environment. We validated our models by confirming two sets of model-generated predictions that were independent from the spatial restraints used in model-building. Detailed analysis of the molecular-dynamics trajectories revealed previously unrecognized KCNQ1/KCNE1 interactions, whose relevance in I(KS) channel function was confirmed by voltage-clamp experiments. Our models and analyses suggest three mechanisms by which KCNE1 slows KCNQ1 activation: by promoting S6 bending at the Pro hinge that closes the activation gate; by promoting a downward movement of gating charge on S4; and by establishing a network of electrostatic interactions with KCNQ1 on the extracellular surface that stabilizes the channel in a pre-open activated state. Our data also suggest how KCNE1 may affect the KCNQ1 pore conductance.
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.