ArticleThe Journal of biological chemistry2014
Coupling of g proteins to reconstituted monomers and tetramers of the M2 muscarinic receptor.
Article in The Journal of biological chemistry, 2014. 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, 36 citations in OpenAlex.
- A critical re-evaluation of the slope factor of the operational model of agonism: When to exponentiate operational efficacy.Scientific reports · 2023Article
- Direct determination of oligomeric organization of integral membrane proteins and lipids from intact customizable bilayer.Nature methods · 2023Article
- Preferential Gs protein coupling of the galanin GalPharmacological research · 2022Article
- Allostery of atypical modulators at oligomeric G protein-coupled receptors.Scientific reports · 2021Article
- Review
- Allosteric Modulation of GPCRs of Class A by Cholesterol.International journal of molecular sciences · 2021Review
- Lipid nanoparticle technologies for the study of G protein-coupled receptors in lipid environments.Biophysical reviews · 2020Review
- Structure and Dynamics of GPCRs in Lipid Membranes: Physical Principles and Experimental Approaches.Molecules (Basel, Switzerland) · 2020Review
- Oligomerization of G protein-coupled receptors: Still doubted?Progress in molecular biology and translational science · 2020Review
- Cryo-EM structure of the native rhodopsin dimer in nanodiscs.The Journal of biological chemistry · 2019Article
- GPCR homo-oligomerization.Current opinion in cell biology · 2019Review
- Toward an understanding of the structural basis of allostery in muscarinic acetylcholine receptors.The Journal of general physiology · 2018Review
- Ligand-Induced Coupling between Oligomers of the MBiophysical journal · 2018Article
- GPCRs and Signal Transducers: Interaction Stoichiometry.Trends in pharmacological sciences · 2018Review
- Muscarinic receptor oligomerization.Neuropharmacology · 2018Review
- Spatial Intensity Distribution Analysis: Studies of G Protein-Coupled Receptor Oligomerisation.Trends in pharmacological sciences · 2018Review
- Quaternary structures of opsin in live cells revealed by FRET spectrometry.The Biochemical journal · 2016Article
- Graded activation and free energy landscapes of a muscarinic G-protein-coupled receptor.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Molecular Pharmacology of δ-Opioid Receptors.Pharmacological reviews · 2016Review
- Dynamic Regulation of Quaternary Organization of the M1 Muscarinic Receptor by Subtype-selective Antagonist Drugs.The Journal of biological chemistry · 2016Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
G protein-coupled receptors can be reconstituted as monomers in nanodiscs and as tetramers in liposomes. When reconstituted with G proteins, both forms enable an allosteric interaction between agonists and guanylyl nucleotides. Both forms, therefore, are candidates for the complex that controls signaling at the level of the receptor. To identify the biologically relevant form, reconstituted monomers and tetramers of the purified M2 muscarinic receptor were compared with muscarinic receptors in sarcolemmal membranes for the effect of guanosine 5'-[β,γ-imido]triphosphate (GMP-PNP) on the inhibition of N-[(3)H]methylscopolamine by the agonist oxotremorine-M. With monomers, a stepwise increase in the concentration of GMP-PNP effected a lateral, rightward shift in the semilogarithmic binding profile (i.e. a progressive decrease in the apparent affinity of oxotremorine-M). With tetramers and receptors in sarcolemmal membranes, GMP-PNP effected a vertical, upward shift (i.e. an apparent redistribution of sites from a state of high affinity to one of low affinity with no change in affinity per se). The data were analyzed in terms of a mechanistic scheme based on a ligand-regulated equilibrium between uncoupled and G protein-coupled receptors (the "ternary complex model"). The model predicts a rightward shift in the presence of GMP-PNP and could not account for the effects at tetramers in vesicles or receptors in sarcolemmal membranes. Monomers present a special case of the model in which agonists and guanylyl nucleotides interact within a complex that is both constitutive and stable. The results favor oligomers of the M2 receptor over monomers as the biologically relevant state for coupling to G proteins.
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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.