ArticleNature structural & molecular biology2022
Anionic lipids unlock the gates of select ion channels in the pacemaker family.
Article in Nature structural & molecular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 36 citations in OpenAlex.
- PIP2 binding at allosteric site blocks activation in human rod CNG channels.Nature communications · 2026Article
- Lipid trapping slows ball-and-chain inactivation in a calcium-activated potassium channel.Nature communications · 2026Article
- Lipid bilayers determine allostery but not intrinsic affinity of cAMP to pacemaker channels.Nature communications · 2026Article
- Mechanism of lipid-dependent cold sensitivity in a model ion channel.Nature communications · 2026Article
- Diverse regulation of functional dimerization of a sugar transporter by different interfacial lipids.Nature communications · 2026Article
- Unveiling Specificity, Redundancy, and Promiscuity of FiveInternational journal of molecular sciences · 2026Article
- Membrane-forming phospholipids allosterically modulate native-state prolyl isomerization in a CNG channel.Protein science : a publication of the Protein Society · 2025Article
- High-Speed Atomic Force Microscopy Reveals the Dynamic Interplay of Membrane Proteins is Lipid-Modulated.Small science · 2025Article
- Lipid transporters E-Syt3 and ORP5 regulate epithelial ion transport by controlling phosphatidylserine enrichment at ER/PM junctions.The EMBO journal · 2025Article
- Regulation of PIEZO1 channel force sensitivity by interblade handshaking.Science advances · 2025Article
- A short intrinsically disordered region at KtrB's N-terminus facilitates allosteric regulation of KNature communications · 2025Article
- Structural basis for malate-driven, pore lipid-regulated activation of the Arabidopsis vacuolar anion channel ALMT9.Nature communications · 2025Article
- Exploring the influence of anionic lipids in the host cell membrane on viral fusion.Biochemical Society transactions · 2024Review
- Membrane lipid nanodomains modulate HCN pacemaker channels in nociceptor DRG neurons.Nature communications · 2024Article
- PIP2 inhibits pore opening of the cyclic nucleotide-gated channel SthK.Nature communications · 2024Article
- Article
- Structural basis for hyperpolarization-dependent opening of human HCN1 channel.Nature communications · 2024Article
- Constitutive activation mechanism of a class C GPCR.Nature structural & molecular biology · 2024Article
- Structural basis of properties, mechanisms, and channelopathy of cyclic nucleotide-gated channels.Channels (Austin, Tex.) · 2023Review
- Direct regulation of the voltage sensor of HCN channels by membrane lipid compartmentalization.Nature communications · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Lipids play important roles in regulating membrane protein function, but the molecular mechanisms used are elusive. Here we investigated how anionic lipids modulate SthK, a bacterial pacemaker channel homolog, and HCN2, whose activity contributes to pacemaking in the heart and brain. Using SthK allowed the reconstitution of purified channels in controlled lipid compositions for functional and structural assays that are not available for the eukaryotic channels. We identified anionic lipids bound tightly to SthK and their exact binding locations and determined that they potentiate channel activity. Cryo-EM structures in the most potentiating lipids revealed an open state and identified a nonannular lipid bound with its headgroup near an intersubunit salt bridge that clamps the intracellular channel gate shut. Breaking this conserved salt bridge abolished lipid modulation in SthK and eukaryotic HCN2 channels, indicating that anionic membrane lipids facilitate channel opening by destabilizing these interactions. Our findings underline the importance of state-dependent protein-lipid interactions.
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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.