ReviewActa pharmacologica Sinica2009
Allosteric activation mechanism of the cys-loop receptors.
Review in Acta pharmacologica Sinica, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Structure of a pH-sensitive pentameric ligand-gated ion channel from the Sarcoptes scabies mite.Nature communications · 2026Article
- Excitatory GABA receptors shape locomotor circuit organization in C. elegans.Scientific reports · 2026Article
- Proteostasis regulation of GABABiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Review
- Structure-function Studies of GABA (A) Receptors and Related computer-aided Studies.Journal of molecular neuroscience : MN · 2023Review
- Structural analysis of pathogenic missense mutations in GABRA2 and identification of a novel de novo variant in the desensitization gate.Molecular genetics & genomic medicine · 2020Article
- Mutational Analysis at Intersubunit Interfaces of an Anionic Glutamate Receptor Reveals a Key Interaction Important for Channel Gating by Ivermectin.Frontiers in molecular neuroscience · 2017Article
- Competitive antagonists facilitate the recovery from desensitization of α1β2γ2 GABAA receptors expressed in Xenopus oocytes.Acta pharmacologica Sinica · 2016Article
- An Electrostatic Funnel in the GABA-Binding Pathway.PLoS computational biology · 2016Article
- Subunit interfaces contribute differently to activation and allosteric modulation of neuronal nicotinic acetylcholine receptors.Neuropharmacology · 2015Article
- Functional Impact of 14 Single Nucleotide Polymorphisms Causing Missense Mutations of Human α7 Nicotinic Receptor.PloS one · 2015Article
- Effects of neuronal nicotinic acetylcholine receptor allosteric modulators in animal behavior studies.Biochemical pharmacology · 2013Review
- The structural mechanism of the Cys-loop receptor desensitization.Molecular neurobiology · 2013Review
- A unified model of the GABA(A) receptor comprising agonist and benzodiazepine binding sites.PloS one · 2013Article
- Incompatibility between a pair of residues from the pre-M1 linker and Cys-loop blocks surface expression of the glycine receptor.The Journal of biological chemistry · 2012Article
- Synaptic neurotransmitter-gated receptors.Cold Spring Harbor perspectives in biology · 2012Review
- Desensitization of alpha7 nicotinic receptor is governed by coupling strength relative to gate tightness.The Journal of biological chemistry · 2011Article
- New insights into the GABA(A) receptor structure and orthosteric ligand binding: receptor modeling guided by experimental data.Proteins · 2011Article
- An Update on GABAρ Receptors.Current neuropharmacology · 2010Article
- Mechanism of Allosteric Modulation of the Cys-loop Receptors.Pharmaceuticals (Basel, Switzerland) · 2010Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Binding of a neurotransmitter to its ionotropic receptor opens a distantly located ion channel, a process termed allosteric activation. Here we review recent advances in the molecular mechanism by which the cys-loop receptors are activated with emphasis on the best studied nicotinic acetylcholine receptors (nAChRs). With a combination of affinity labeling, mutagenesis, electrophysiology, kinetic modeling, electron microscopy (EM), and crystal structure analysis, the allosteric activation mechanism is emerging. Specifically, the binding domain and gating domain are interconnected by an allosteric activation network. Agonist binding induces conformational changes, resulting in the rotation of a beta sheet of amino-terminal domain and outward movement of loop 2, loop F, and cys-loop, which are coupled to the M2-M3 linker to pull the channel to open. However, there are still some controversies about the movement of the channel-lining domain M2. Nine angstrom resolution EM structure of a nAChR imaged in the open state suggests that channel opening is the result of rotation of the M2 domain. In contrast, recent crystal structures of bacterial homologues of the cys-loop receptor family in apparently open state have implied an M2 tilting model with pore dilation and quaternary twist of the whole pentameric receptor. An elegant study of the nAChR using protonation scanning of M2 domain supports a similar pore dilation activation mechanism with minimal rotation of M2. This remains to be validated with other approaches including high resolution structure determination of the mammalian cys-loop receptors in the open state.
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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.