ArticleProceedings of the National Academy of Sciences of the United States of America2013
Structure of the C-terminal region of an ERG channel and functional implications.
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 53 papers.
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Who cites it
53 citing papers in PubMed, 64 citations in OpenAlex.
- Forward genetics reveals a conserved CNBHD-CNBHD interface that restrains EAG channel activation to regulate sleep.PLoS genetics · 2026Article
- The PAS domain directly regulates hERG channel gating in patch-clamp fluorometry recordings.Biophysical journal · 2026Article
- Chlorpromazine inhibits EAG1 channels by altering the interdomain coupling.Biophysical journal · 2026Article
- Molecular Determinants of Voltage-Dependent Gating in Kv11.1 Channels.Advances in experimental medicine and biology · 2026Review
- An Allosteric Model for Electromechanical Coupling in Cardiac CNBD Channels.bioRxiv : the preprint server for biology · 2025Article
- GORK KNature communications · 2025Article
- Review
- Photoinhibition of the hERG potassium channel PAS domain by ultraviolet light speeds channel closing.Biophysical journal · 2024Article
- Use of Surface Plasmon Resonance Technique for Studies of Inter-domain Interactions in Ion Channels.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Non-missense variants of KCNH2 show better outcomes in type 2 long QT syndrome.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 · 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
- The ERG1 KFrontiers in molecular neuroscience · 2022Review
- 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
- Long QT syndrome - Bench to bedside.Heart rhythm O2 · 2021Article
- Gating and regulation of KCNH (ERG, EAG, and ELK) channels by intracellular domains.Channels (Austin, Tex.) · 2020Review
- Structure of KCNH2 cyclic nucleotide-binding homology domain reveals a functionally vital salt-bridge.The Journal of general physiology · 2020Article
- Modulation of hERG KFrontiers in pharmacology · 2020Review
- The hERG potassium channel intrinsic ligand regulates N- and C-terminal interactions and channel closure.The Journal of general physiology · 2019Article
- N- and C-terminal interactions in KCNH channels: The spotlight on the intrinsic ligand.The Journal of general physiology · 2019Article
- Extracellular protons accelerate hERG channel deactivation by destabilizing voltage sensor relaxation.The Journal of general physiology · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The human ether-à-go-go-related gene (hERG) encodes a K(+) channel crucial for repolarization of the cardiac action potential. EAG-related gene (ERG) channels contain a C-terminal cyclic nucleotide-binding homology domain coupled to the pore of the channel by a C-linker. Here, we report the structure of the C-linker/cyclic nucleotide-binding homology domain of a mosquito ERG channel at 2.5-Å resolution. The structure reveals that the region expected to form the cyclic nucleotide-binding pocket is negatively charged and is occupied by a short β-strand, referred to as the intrinsic ligand, explaining the lack of direct regulation of ERG channels by cyclic nucleotides. In hERG channels, the intrinsic ligand harbors hereditary mutations associated with long-QT syndrome (LQTS), a potentially lethal cardiac arrhythmia. Mutations in the intrinsic ligand affected hERG channel gating and LQTS mutations abolished hERG currents and altered trafficking of hERG channels, which explains the LQT phenotype. The structure also reveals a dramatically different conformation of the C-linker compared with the structures of the related ether-à-go-go-like K(+) and hyperpolarization-activated cyclic nucleotide-modulated channels, suggesting that the C-linker region may be highly dynamic in the KCNH, hyperpolarization-activated cyclic nucleotide-modulated, and cyclic nucleotide-gated channels.
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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.