ArticleScience (New York, N.Y.)2015
K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac.
Article in Science (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers.
What it found
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Who cites it
191 citing papers in PubMed, 308 citations in OpenAlex.
- One pocket to activate them all (?): Efforts on understanding the modulator pocket in K2P channels.Channels (Austin, Tex.) · 2026Review
- Role for TREK-1 as a polymodal sensor and regulator of cell activity.Channels (Austin, Tex.) · 2026Review
- Mechanisms of intracellular pH gating and local anesthetic inhibition of the two-pore domain KProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cross-talk of filter gate and lower helices drives polymodal regulation and disease in TREK channels.Nature communications · 2026Article
- Mechanistical and structural basis of Kv channel inhibition by 4-aminopyridine.bioRxiv : the preprint server for biology · 2026Article
- Gating crosstalk in potassium channels.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Structural basis of the gating mechanism of the large-conductance mechanosensitive channel from Escherichia coli.Nature communications · 2026Article
- An Atomically Dispersed Copper-Catalyst Lights the Way to Selective N-Demethylations.Nature communications · 2026Article
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- Structural evidence that a lipid plug controls KNature communications · 2026Article
- The Converging Effects of Different Categories of Antidepressants on the Brain: A Systematic Meta-Analysis of Public Transcriptional Profiling Data from the Hippocampus and Cortex.bioRxiv : the preprint server for biology · 2026Article
- Molecular architecture of the fungal-specific potassium channel TOK1.Nature communications · 2026Article
- Swapped and non-swapped TRAAK states co-exist in membranes at a ratio influenced by temperature.Nature communications · 2026Article
- Insights into the structure and modulation of human TWIK-2.Nature communications · 2026Article
- Light-induced analgesia provides a drug-free optical method for pain relief via activation of TRAAK kNature communications · 2026Article
- Toward the rational design of oncogenic TASK-3 channel inhibitor peptides and nanoconjugate complexes.Frontiers in pharmacology · 2026Review
- From Selective Permeation to Physiology in Potassium Channels.Function (Oxford, England) · 2025Review
- Atomistic mechanism of noncanonical voltage gating in KScience advances · 2025Article
- The potassium channel KNature communications · 2025Article
- Evaluation of Small-Molecule Binding Site Prediction Methods on Membrane-Embedded Protein Interfaces.Journal of chemical information and modeling · 2025Article
131 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
TREK-2 (KCNK10/K2P10), a two-pore domain potassium (K2P) channel, is gated by multiple stimuli such as stretch, fatty acids, and pH and by several drugs. However, the mechanisms that control channel gating are unclear. Here we present crystal structures of the human TREK-2 channel (up to 3.4 angstrom resolution) in two conformations and in complex with norfluoxetine, the active metabolite of fluoxetine (Prozac) and a state-dependent blocker of TREK channels. Norfluoxetine binds within intramembrane fenestrations found in only one of these two conformations. Channel activation by arachidonic acid and mechanical stretch involves conversion between these states through movement of the pore-lining helices. These results provide an explanation for TREK channel mechanosensitivity, regulation by diverse stimuli, and possible off-target effects of the serotonin reuptake inhibitor Prozac.
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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.