ArticlePloS one2011
The N-terminal tail of hERG contains an amphipathic α-helix that regulates channel deactivation.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 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
61 citing papers in PubMed, 81 citations in OpenAlex.
- Molecular Determinants of Voltage-Dependent Gating in Kv11.1 Channels.Advances in experimental medicine and biology · 2026Review
- Photoinhibition of the hERG potassium channel PAS domain by ultraviolet light speeds channel closing.Biophysical journal · 2024Article
- A hydrophobic nexus at the heart of hERG K channel gating.Biophysical journal · 2024Article
- An intracellular hydrophobic nexus critical for hERG1 channel slow deactivation.Biophysical journal · 2024Article
- An Insight into the Potassium Currents of hERG and Their Simulation.Molecules (Basel, Switzerland) · 2023Article
- Binding of RPR260243 at the intracellular side of the hERG1 channel pore domain slows closure of the helix bundle crossing gate.Frontiers in molecular biosciences · 2023Article
- Conformation-sensitive antibody reveals an altered cytosolic PAS/CNBh assembly during hERG channel gating.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Molecular Insights Into the Gating Kinetics of the Cardiac hERG Channel, Illuminated by Structure and Molecular Dynamics.Frontiers in pharmacology · 2021Review
- Gating and regulation of KCNH (ERG, EAG, and ELK) channels by intracellular domains.Channels (Austin, Tex.) · 2020Review
- Discovery of a heme-binding domain in a neuronal voltage-gated potassium channel.The Journal of biological chemistry · 2020Article
- The EAG Voltage-Dependent KFrontiers in pharmacology · 2020Review
- Modulation of hERG KFrontiers in pharmacology · 2020Review
- Article
- Voltage-dependent activation in EAG channels follows a ligand-receptor rather than a mechanical-lever mechanism.The Journal of biological chemistry · 2019Article
- The hERG potassium channel intrinsic ligand regulates N- and C-terminal interactions and channel closure.The Journal of general physiology · 2019Article
- Extracellular protons accelerate hERG channel deactivation by destabilizing voltage sensor relaxation.The Journal of general physiology · 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
- Relative positioning of Kv11.1 (hERG) KScientific reports · 2018Article
- Two mutations at different positions in the CNBH domain of the hERG channel accelerate deactivation and impair the interaction with the EAG domain.The Journal of physiology · 2018Article
- Functional characterization of Kv11.1 (hERG) potassium channels split in the voltage-sensing domain.Pflugers Archiv : European journal of physiology · 2018Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cytoplasmic N-terminal domain of the human ether-a-go-go related gene (hERG) K+ channel is critical for the slow deactivation kinetics of the channel. However, the mechanism(s) by which the N-terminal domain regulates deactivation remains to be determined. Here we show that the solution NMR structure of the N-terminal 135 residues of hERG contains a previously described Per-Arnt-Sim (PAS) domain (residues 26-135) as well as an amphipathic α-helix (residues 13-23) and an initial unstructured segment (residues 2-9). Deletion of residues 2-25, only the unstructured segment (residues 2-9) or replacement of the α-helix with a flexible linker all result in enhanced rates of deactivation. Thus, both the initial flexible segment and the α-helix are required but neither is sufficient to confer slow deactivation kinetics. Alanine scanning mutagenesis identified R5 and G6 in the initial flexible segment as critical for slow deactivation. Alanine mutants in the helical region had less dramatic phenotypes. We propose that the PAS domain is bound close to the central core of the channel and that the N-terminal α-helix ensures that the flexible tail is correctly orientated for interaction with the activation gating machinery to stabilize the open state of the channel.
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.