ArticleBiophysical journal2014
Proline scan of the HERG channel S6 helix reveals the location of the intracellular pore gate.
Article in Biophysical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 49 citations in OpenAlex.
- Molecular Determinants of Voltage-Dependent Gating in Kv11.1 Channels.Advances in experimental medicine and biology · 2026Review
- Article
- Harnessing AlphaFold to reveal hERG channel conformational state secrets.bioRxiv : the preprint server for biology · 2025Article
- An LQT2-related mutation in the voltage-sensing domain is involved in switching the gating polarity of hERG.BMC biology · 2024Article
- The mechanism study ofTranslational cancer research · 2022Article
- Mapping Electromechanical Coupling Pathways in Voltage-Gated Ion Channels: Challenges and the Way Forward.Journal of molecular biology · 2021Review
- Atomistic Insights of Calmodulin Gating of Complete Ion Channels.International journal of molecular sciences · 2020Review
- The EAG Voltage-Dependent KFrontiers in pharmacology · 2020Review
- Modulation of hERG KFrontiers in pharmacology · 2020Review
- Identification of undecylenic acid as EAG channel inhibitor using surface plasmon resonance-based screen of KCNH channels.BMC pharmacology & toxicology · 2019Article
- Voltage-dependent activation in EAG channels follows a ligand-receptor rather than a mechanical-lever mechanism.The Journal of biological chemistry · 2019Article
- New Structures and Gating of Voltage-Dependent Potassium (Kv) Channels and Their Relatives: A Multi-Domain and Dynamic Question.International journal of molecular sciences · 2019Review
- Investigating the state dependence of drug binding in hERG channels using a trapped-open channel phenotype.Scientific reports · 2018Article
- Structural insights into the mechanisms of CNBD channel function.The Journal of general physiology · 2018Review
- A new mechanism of voltage-dependent gating exposed by KThe Journal of general physiology · 2017Article
- Eag1 Voltage-Dependent Potassium Channels: Structure, Electrophysiological Characteristics, and Function in Cancer.The Journal of membrane biology · 2017Review
- hERG S4-S5 linker acts as a voltage-dependent ligand that binds to the activation gate and locks it in a closed state.Scientific reports · 2017Article
- Stabilization of the Activated hERG Channel Voltage Sensor by Depolarization Involves the S4-S5 Linker.Biophysical journal · 2017Article
- Conservation analysis of residues in the S4-S5 linker and the terminal part of the S5-P-S6 pore modulus in Kv and HCN channels: flexible determinants for the electromechanical coupling.Pflugers Archiv : European journal of physiology · 2015Article
- Voltage-dependent gating of KCNH potassium channels lacking a covalent link between voltage-sensing and pore domains.Nature communications · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In Shaker-like channels, the activation gate is formed at the bundle crossing by the convergence of the inner S6 helices near a conserved proline-valine-proline motif, which introduces a kink that allows for electromechanical coupling with voltage sensor motions via the S4-S5 linker. Human ether-a-go-go-related gene (hERG) channels lack the proline-valine-proline motif and the location of the intracellular pore gate and how it is coupled to S4 movement is less clear. Here, we show that proline substitutions within the S6 of hERG perturbed pore gate closure, trapping channels in the open state. Performing a proline scan of the inner S6 helix, from Ile(655) to Tyr(667) revealed that gate perturbation occurred with proximal (I655P-Q664P), but not distal (R665P-Y667P) substitutions, suggesting that Gln(664) marks the position of the intracellular gate in hERG channels. Using voltage-clamp fluorimetry and gating current analysis, we demonstrate that proline substitutions trap the activation gate open by disrupting the coupling between the voltage-sensing unit and the pore of the channel. We characterize voltage sensor movement in one such trapped-open mutant channel and demonstrate the kinetics of what we interpret to be intrinsic hERG voltage sensor movement.
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.