ArticleNature2014
Physical mechanism for gating and mechanosensitivity of the human TRAAK K+ channel.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 194 papers.
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Who cites it
194 citing papers in PubMed, 340 citations in OpenAlex.
- One pocket to activate them all (?): Efforts on understanding the modulator pocket in K2P channels.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
- BRET-Based Approaches for Ion Channels: Emerging Applications and Future Directions.Archiv der Pharmazie · 2026Review
- Shared-Scale Predictive Benchmarking of an Acoustic-Radiation-Force Model for Frequency-Dependent Retinal Ganglion Cell Responses.Bioengineering (Basel, Switzerland) · 2026Article
- A two-step clockwork mechanism opens a proteo-lipidic pore in PIEZO2.Nature chemical biology · 2026Article
- Ion-electron coupling-enabled mechanical ion transistor with ultralow subthreshold swing.Science advances · 2026Article
- Structural basis of lipid-dependent allosteric gating mechanisms for PC1-PC2 ion channel.Nature communications · 2026Article
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- Structural evidence that a lipid plug controls KNature communications · 2026Article
- Tension TRAAKer: a chemigenetic fluorescent membrane tension reporter.bioRxiv : the preprint server for biology · 2026Article
- Hysteretic Conductance in Ion Channel Gating.Entropy (Basel, Switzerland) · 2026Review
- 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
- Lipid Regulation of Mechanosensitive Ion Channels.International journal of molecular sciences · 2026Review
- 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
- The cornea-trigeminal axis: potassium channels as master regulators of ocular surface homeostasis and sensory transduction.Frontiers in cell and developmental biology · 2026Review
- The Nanodisc System for Investigating Protein-Lipid Interactions.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Atomistic mechanism of noncanonical voltage gating in KScience advances · 2025Article
- Unnatural Amino Acid Photo-Crosslinking Sheds Light on Gating of the Mechanosensitive Ion Channel OSCA1.2.International journal of molecular sciences · 2025Article
134 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Activation of mechanosensitive ion channels by physical force underlies many physiological processes including the sensation of touch, hearing and pain. TRAAK (also known as KCNK4) ion channels are neuronally expressed members of the two-pore domain K(+) (K2P) channel family and are mechanosensitive. They are involved in controlling mechanical and temperature nociception in mice. Mechanosensitivity of TRAAK is mediated directly through the lipid bilayer--it is a membrane-tension-gated channel. However, the molecular mechanism of TRAAK channel gating and mechanosensitivity is unknown. Here we present crystal structures of TRAAK in conductive and non-conductive conformations defined by the presence of permeant ions along the conduction pathway. In the non-conductive state, a lipid acyl chain accesses the channel cavity through a 5 Å-wide lateral opening in the membrane inner leaflet and physically blocks ion passage. In the conductive state, rotation of a transmembrane helix (TM4) about a central hinge seals the intramembrane opening, preventing lipid block of the cavity and permitting ion entry. Additional rotation of a membrane interacting TM2-TM3 segment, unique to mechanosensitive K2Ps, against TM4 may further stabilize the conductive conformation. Comparison of the structures reveals a biophysical explanation for TRAAK mechanosensitivity--an expansion in cross-sectional area up to 2.7 nm(2) in the conductive state is expected to create a membrane-tension-dependent energy difference between conformations that promotes force activation. Our results show how tension of the lipid bilayer can be harnessed to control gating and mechanosensitivity of a eukaryotic ion channel.
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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.