ArticleThe Journal of general physiology2021
Identification of PUFA interaction sites on the cardiac potassium channel KCNQ1.
Article in The Journal of general physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- A mechanistic understanding of how KCNE1 tunes KCNQ1 channel pharmacology.Structure (London, England : 1993) · 2026Article
- PUFA modulation of ASIC3 involves both specific and lipid solvent-like interactions.bioRxiv : the preprint server for biology · 2026Article
- KCNQ1 and PIPCell research · 2025Article
- Associations of Serum n-6 Polyunsaturated Fatty Acid Concentrations with Heart Rate-Corrected QT and JT Intervals in Middle-Aged Males.The Journal of nutrition · 2025Article
- Secondary structure transitions and dual PIP2 binding define cardiac KCNQ1-KCNE1 channel gating.Cell research · 2025Article
- From Selective Permeation to Physiology in Potassium Channels.Function (Oxford, England) · 2025Review
- Beneficial action potential duration-shortening effects, but deleterious negative inotropism of IKs-activator docosahexaenoyl glycine in long QT syndrome type 2.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 · 2025Article
- Effects of dietary long-chain polyunsaturated fatty acids on osmoregulation and salinity adaptation in red tilapia (Oreochromis mossambicus♀ × O. niloticus♂) under salinity stress.Fish physiology and biochemistry · 2025Article
- Structure of the human KNature structural & molecular biology · 2025Article
- Molecular Insights into Single-Chain Lipid Modulation of Acid-Sensing Ion Channel 3.The journal of physical chemistry. B · 2024Article
- The endocannabinoid ARA-S facilitates the activation of cardiac Kv7.1/KCNE1 channels from different species.Channels (Austin, Tex.) · 2024Article
- Article
- Lipophilic compounds restore function to neurodevelopmental-associated KCNQ3 mutations.Communications biology · 2024Article
- Molecular Insights into Single Chain Lipid Modulation of Acid-Sensing Ion Channel 3.bioRxiv : the preprint server for biology · 2024Article
- Activation of hTREK-1 by polyunsaturated fatty acids involves direct interaction.Scientific reports · 2024Article
- Carboxyl-group compounds activate voltage-gated potassium channels via a distinct mechanism.The Journal of general physiology · 2024Article
- Structure of the human KbioRxiv : the preprint server for biology · 2024Article
- Mechanistic understanding of KCNQ1 activating polyunsaturated fatty acid analogs.The Journal of general physiology · 2023Article
- Mechanistic insights into robust cardiac IeLife · 2023Article
- Mechanistic insights into robust cardiac IbioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Polyunsaturated fatty acids (PUFAs), but not saturated fatty acids, modulate ion channels such as the cardiac KCNQ1 channel, although the mechanism is not completely understood. Using both simulations and experiments, we find that PUFAs interact directly with the KCNQ1 channel via two different binding sites: one at the voltage sensor and one at the pore. These two amphiphilic binding pockets stabilize the negatively charged PUFA head group by electrostatic interactions with R218, R221, and K316, while the hydrophobic PUFA tail is selectively stabilized by cassettes of hydrophobic residues. The rigid saturated tail of stearic acid prevents close contacts with KCNQ1. By contrast, the mobile tail of PUFA linoleic acid can be accommodated in the crevice of the hydrophobic cassette, a defining feature of PUFA selectivity in KCNQ1. In addition, we identify Y268 as a critical PUFA anchor point underlying fatty acid selectivity. Combined, this study provides molecular models of direct interactions between PUFAs and KCNQ1 and identifies selectivity mechanisms. Long term, this understanding may open new avenues for drug development based on PUFA mechanisms.
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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.