ArticleNature2012
Structure and dynamics of the M3 muscarinic acetylcholine receptor.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 352 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
352 citing papers in PubMed, 1 synthesis or guideline pooled it, 806 citations in OpenAlex.
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- Chlorogenic acid reduces Lipopolysaccharide-Induced intestinal inflammation through Inhibition of acetylcholinesterase and activation of muscarinic receptors.Molecular biology reports · 2025Article
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- Ultrasensitive label-free optical recording of bioelectric potentials using dioxythiophene-based electrochromic polymers.Nature communications · 2025Article
- Adiabatic-Bias Molecular Dynamics Simulations Reveal the Impact of Mutations on Muscarinic Antagonist Unbinding Kinetics.Journal of chemical information and modeling · 2025Article
- Christian Bohr. Discoverer of Homotropic and Heterotopic Allostery: Periods Leading up to Bohr's Life, Work, and Beyond. Was Bohr a Vitalist and Right About a "Specific Activity"?Acta physiologica (Oxford, England) · 2025Review
- Development of Mutant MBiochemistry · 2025Article
292 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Acetylcholine, the first neurotransmitter to be identified, exerts many of its physiological actions via activation of a family of G-protein-coupled receptors (GPCRs) known as muscarinic acetylcholine receptors (mAChRs). Although the five mAChR subtypes (M1-M5) share a high degree of sequence homology, they show pronounced differences in G-protein coupling preference and the physiological responses they mediate. Unfortunately, despite decades of effort, no therapeutic agents endowed with clear mAChR subtype selectivity have been developed to exploit these differences. We describe here the structure of the G(q/11)-coupled M3 mAChR ('M3 receptor', from rat) bound to the bronchodilator drug tiotropium and identify the binding mode for this clinically important drug. This structure, together with that of the G(i/o)-coupled M2 receptor, offers possibilities for the design of mAChR subtype-selective ligands. Importantly, the M3 receptor structure allows a structural comparison between two members of a mammalian GPCR subfamily displaying different G-protein coupling selectivities. Furthermore, molecular dynamics simulations suggest that tiotropium binds transiently to an allosteric site en route to the binding pocket of both receptors. These simulations offer a structural view of an allosteric binding mode for an orthosteric GPCR ligand and provide additional opportunities for the design of ligands with different affinities or binding kinetics for different mAChR subtypes. Our findings not only offer insights into the structure and function of one of the most important GPCR families, but may also facilitate the design of improved therapeutics targeting these critical receptors.
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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.