ArticleNature2012
Structure of the carboxy-terminal region of a KCNH channel.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 119 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
- Encapsulins in Terpene Biosynthesis: Enzyme Nanoreactors in Bacterial Secondary Metabolism.Biochemistry · 2026Review
- A Historical Outline of Fluorescence Spectroscopy in Ion Channel Research.Advances in experimental medicine and biology · 2026Review
- 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
- Structural basis for the activity regulation of Medicago calcium channel CNGC15.Cell discovery · 2025Article
- GORK KNature communications · 2025Article
- The biosynthesis of the odorant 2-methylisoborneol is compartmentalized inside a protein shell.Nature communications · 2024Article
- Photoinhibition of the hERG potassium channel PAS domain by ultraviolet light speeds channel closing.Biophysical journal · 2024Article
- The biosynthesis of the odorant 2-methylisoborneol is compartmentalized inside a protein shell.bioRxiv : the preprint server for biology · 2024Article
- Use of Surface Plasmon Resonance Technique for Studies of Inter-domain Interactions in Ion Channels.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Transfer RNA-mediated restoration of potassium current and electrical correction in premature termination long-QT syndrome hERG mutants.Molecular therapy. Nucleic acids · 2023Article
- Genome-Scale Analysis Reveals Extensive Diversification of Voltage-Gated K+ Channels in Stem Cnidarians.Genome biology and evolution · 2023Article
- Article
- Structural basis for the activity regulation of a potassium channel AKT1 from Arabidopsis.Nature communications · 2022Article
- 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
- External Cd2+ and protons activate the hyperpolarization-gated K+ channel KAT1 at the voltage sensor.The Journal of general physiology · 2021Article
33 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
4 authors at 2 institutions in 1 country.
Funding
Abstract
The KCNH family of ion channels, comprising ether-à-go-go (EAG), EAG-related gene (ERG), and EAG-like (ELK) K(+)-channel subfamilies, is crucial for repolarization of the cardiac action potential, regulation of neuronal excitability and proliferation of tumour cells. The carboxy-terminal region of KCNH channels contains a cyclic-nucleotide-binding homology domain (CNBHD) and C-linker that couples the CNBHD to the pore. The C-linker/CNBHD is essential for proper function and trafficking of ion channels in the KCNH family. However, despite the importance of the C-linker/CNBHD for the function of KCNH channels, the structural basis of ion-channel regulation by the C-linker/CNBHD is unknown. Here we report the crystal structure of the C-linker/CNBHD of zebrafish ELK channels at 2.2-Å resolution. Although the overall structure of the C-linker/CNBHD of ELK channels is similar to the cyclic-nucleotide-binding domain (CNBD) structure of the related hyperpolarization-activated cyclic-nucleotide-modulated (HCN) channels, there are marked differences. Unlike the CNBD of HCN, the CNBHD of ELK displays a negatively charged electrostatic profile that explains the lack of binding and regulation of KCNH channels by cyclic nucleotides. Instead of cyclic nucleotide, the binding pocket is occupied by a short β-strand. Mutations of the β-strand shift the voltage dependence of activation to more depolarized voltages, implicating the β-strand as an intrinsic ligand for the CNBHD of ELK channels. In both ELK and HCN channels the C-linker is the site of virtually all of the intersubunit interactions in the C-terminal region. However, in the zebrafish ELK structure there is a reorientation in the C-linker so that the subunits form dimers instead of tetramers, as observed in HCN channels. These results provide a structural framework for understanding the regulation of ion channels in the KCNH family by the C-linker/CNBHD and may guide the design of specific drugs.
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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.