ArticleThe Journal of biological chemistry2015
Intramembrane aromatic interactions influence the lipid sensitivities of pentameric ligand-gated ion channels.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 56 citations in OpenAlex.
- Structure-Function Studies of Pentameric Ligand-Gated Ion Channels: Combining Experimental and Computational Approaches.Advances in experimental medicine and biology · 2026Review
- Asymmetric gating of a homopentameric ion channel GLIC revealed by cryo-EM.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structural mechanism of lipid modulation of pentameric ligand-gated ion channel activity.bioRxiv : the preprint server for biology · 2025Article
- Article
- Ion transport in muscle acetylcholine receptor maintained by conserved salt bridges between the pore and lipid membrane.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- State-dependent binding of cholesterol and an anionic lipid to the muscle-type Torpedo nicotinic acetylcholine receptor.Communications biology · 2024Article
- Cryo-EM structures of prokaryotic ligand-gated ion channel GLIC provide insights into gating in a lipid environment.Nature communications · 2024Article
- Discovery of lipid binding sites in a ligand-gated ion channel by integrating simulations and cryo-EM.eLife · 2024Article
- Macromolecular rate theory explains the temperature dependence of membrane conductance kinetics.Biophysical journal · 2023Article
- Open-channel structure of a pentameric ligand-gated ion channel reveals a mechanism of leaflet-specific phospholipid modulation.Nature communications · 2022Article
- Positive Allosteric Modulators of Glycine Receptors and Their Potential Use in Pain Therapies.Pharmacological reviews · 2022Review
- Recent Insight into Lipid Binding and Lipid Modulation of Pentameric Ligand-Gated Ion Channels.Biomolecules · 2022Review
- Article
- State-dependent protein-lipid interactions of a pentameric ligand-gated ion channel in a neuronal membrane.PLoS computational biology · 2021Article
- Ion channels as lipid sensors: from structures to mechanisms.Nature chemical biology · 2020Review
- The functional role of the αM4 transmembrane helix in the muscle nicotinic acetylcholine receptor probed through mutagenesis and coevolutionary analyses.The Journal of biological chemistry · 2020Article
- Cryo-EM structures of a lipid-sensitive pentameric ligand-gated ion channel embedded in a phosphatidylcholine-only bilayer.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- A lipid site shapes the agonist response of a pentameric ligand-gated ion channel.Nature chemical biology · 2019Article
- Article
- Direct visualization of ion-channel gating in a native environment.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Although the Torpedo nicotinic acetylcholine receptor (nAChR) reconstituted into phosphatidylcholine (PC) membranes lacking cholesterol and anionic lipids adopts a conformation where agonist binding is uncoupled from channel gating, the underlying mechanism remains to be defined. Here, we examine the mechanism behind lipid-dependent uncoupling by comparing the propensities of two prokaryotic homologs, Gloebacter and Erwinia ligand-gated ion channel (GLIC and ELIC, respectively), to adopt a similar uncoupled conformation. Membrane-reconstituted GLIC and ELIC both exhibit folded structures in the minimal PC membranes that stabilize an uncoupled nAChR. GLIC, with a large number of aromatic interactions at the interface between the outermost transmembrane α-helix, M4, and the adjacent transmembrane α-helices, M1 and M3, retains the ability to flux cations in this uncoupling PC membrane environment. In contrast, ELIC, with a level of aromatic interactions intermediate between that of the nAChR and GLIC, does not undergo agonist-induced channel gating, although it does not exhibit the expected biophysical characteristics of the uncoupled state. Engineering new aromatic interactions at the M4-M1/M3 interface to promote effective M4 interactions with M1/M3, however, increases the stability of the transmembrane domain to restore channel function. Our data provide direct evidence that M4 interactions with M1/M3 are modulated during lipid sensing. Aromatic residues strengthen M4 interactions with M1/M3 to reduce the sensitivities of pentameric ligand-gated ion channels to their surrounding membrane environment.
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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.