ArticleCell research2021
Molecular basis for ligand activation of the human KCNQ2 channel.
Article in Cell research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 132 citations in OpenAlex.
- Structural and kinetic mechanisms of state-dependent potassium channel inhibition.Science advances · 2026Article
- Voltage-sensor conformational microenvironments encode isoform-selective ion channel activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Ganoderic Acid A Ameliorates Pentylenetetrazol-Induced Epilepsy in Mice via Activating KCNQ2.CNS neuroscience & therapeutics · 2026Article
- The SIMDA framework maps PIP2-binding sites regulating the KCNQ1 channel.Nature communications · 2026Article
- Structural basis of the neuronal M-current generated by an asymmetric KCNQ2/3 assembly.Cell research · 2026Article
- Cannabidiol inhibits both human KActa pharmacologica Sinica · 2026Article
- From Retigabine to Azetukalner: Reviving Voltage-Gated Potassium Channels for Epilepsy Therapy.Archiv der Pharmazie · 2026Review
- Calmodulin assists during co-translational folding of the KProtein science : a publication of the Protein Society · 2026Article
- Coupling of functionality to trafficking of KCNQ2/3 potassium channels at the axon initial segment.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Galangin, a novel Kv7 potassium channel opener, exerts potent antinociceptive effects in multiple chronic pain mouse models.Acta pharmacologica Sinica · 2026Article
- Molecular dynamics of the pathogenic KCNQ2 variant G256W reveal mechanisms of channel dysfunction in epileptic encephalopathy.bioRxiv : the preprint server for biology · 2025Article
- Biophysical and structural mechanisms of epilepsy-associated mutations in the S4-S5 Linker of KCNQ2 channels.Channels (Austin, Tex.) · 2025Article
- Recent advances in the pharmacology of voltage-gated ion channels.Pharmacological reviews · 2025Review
- Pharmacological Actions of Potassium Channel Openers on Voltage-Gated Potassium Channels.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Evaluation of Small-Molecule Binding Site Prediction Methods on Membrane-Embedded Protein Interfaces.Journal of chemical information and modeling · 2025Article
- Small molecule inhibits KCNQ channels with a non-blocking mechanism.Nature chemical biology · 2025Article
- Phosphatidylinositol 4,5-bisphosphate activation mechanism of human KCNQ5.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The conductance of KCNQ2 and its pathogenic variants is determined by individual subunit gating.Science advances · 2025Article
- Targeting Kv7 Potassium Channels for Epilepsy.CNS drugs · 2025Review
- A Novel Compound QO-83 Alleviates Acute and Chronic Epileptic Seizures in Rodents by Modulating KCNS neuroscience & therapeutics · 2025Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The voltage-gated potassium channel KCNQ2 is responsible for M-current in neurons and is an important drug target to treat epilepsy, pain and several other diseases related to neuronal hyper-excitability. A list of synthetic compounds have been developed to directly activate KCNQ2, yet our knowledge of their activation mechanism is limited, due to lack of high-resolution structures. Here, we report cryo-electron microscopy (cryo-EM) structures of the human KCNQ2 determined in apo state and in complex with two activators, ztz240 or retigabine, which activate KCNQ2 through different mechanisms. The activator-bound structures, along with electrophysiology analysis, reveal that ztz240 binds at the voltage-sensing domain and directly stabilizes it at the activated state, whereas retigabine binds at the pore domain and activates the channel by an allosteric modulation. By accurately defining ligand-binding sites, these KCNQ2 structures not only reveal different ligand recognition and activation mechanisms, but also provide a structural basis for drug optimization and design.
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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.