ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012
Structural aspects of M₃ muscarinic acetylcholine receptor dimer formation and activation.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- A critical re-evaluation of the slope factor of the operational model of agonism: When to exponentiate operational efficacy.Scientific reports · 2023Article
- Preassembled GPCR signaling complexes mediate distinct cellular responses to ultralow ligand concentrations.Science signaling · 2018Article
- Muscarinic receptor oligomerization.Neuropharmacology · 2018Review
- Spatial Intensity Distribution Analysis: Studies of G Protein-Coupled Receptor Oligomerisation.Trends in pharmacological sciences · 2018Review
- BetaBiochimica et biophysica acta. Biomembranes · 2017Article
- Differential Contribution of Transmembrane Domains IV, V, VI, and VII to Human Angiotensin II Type 1 Receptor Homomer Formation.The Journal of biological chemistry · 2017Article
- Recent Advances and Applications of Molecular Docking to G Protein-Coupled Receptors.Molecules (Basel, Switzerland) · 2017Review
- The Serotonin Receptor Subtype 5b Specifically Interacts with Serotonin Receptor Subtype 1A.Frontiers in molecular neuroscience · 2017Article
- Dynamic Regulation of Quaternary Organization of the M1 Muscarinic Receptor by Subtype-selective Antagonist Drugs.The Journal of biological chemistry · 2016Article
- Molecular dynamics simulations and structure-based network analysis reveal structural and functional aspects of G-protein coupled receptor dimer interactions.Journal of computer-aided molecular design · 2016Article
- Distinct Agonist Regulation of Muscarinic Acetylcholine M2-M3 Heteromers and Their Corresponding Homomers.The Journal of biological chemistry · 2015Article
- Helix 8 and the i3 loop of the muscarinic M3 receptor are crucial sites for its regulation by the Gβ5-RGS7 complex.Biochemistry · 2015Article
- Transmembrane domains of attraction on the TSH receptor.Endocrinology · 2015Article
- CrossTalk opposing view: Weighing the evidence for class A GPCR dimers, the jury is still out.The Journal of physiology · 2014Article
- Allosteric interactions at adenosine A(1) and A(3) receptors: new insights into the role of small molecules and receptor dimerization.British journal of pharmacology · 2014Review
- Differential stability of the crystallographic interfaces of mu- and kappa-opioid receptors.PloS one · 2014Article
- G protein-coupled receptor oligomerization revisited: functional and pharmacological perspectives.Pharmacological reviews · 2014Review
- Novel structural and functional insights into M3 muscarinic receptor dimer/oligomer formation.The Journal of biological chemistry · 2013Article
- Molecular modeling studies give hint for the existence of a symmetric hβ₂R-Gαβγ-homodimer.Journal of molecular modeling · 2013Article
- The prevalence, maintenance, and relevance of G protein-coupled receptor oligomerization.Molecular pharmacology · 2013Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
To explore the structural mechanisms underlying the assembly and activation of family A GPCR dimers, we used the rat M(3) muscarinic acetylcholine receptor (M3R) as a model system. Studies with Cys-substituted mutant M3Rs expressed in COS-7 cells led to the identification of several mutant M3Rs that exclusively existed as cross-linked dimers under oxidizing conditions. The cross-linked residues were located at the bottom of transmembrane domain 5 (TM5) and within the N-terminal portion of the third intracellular loop (i3 loop). Studies with urea-stripped membranes demonstrated that M3R disulfide cross-linking did not require the presence of heterotrimeric G proteins. Molecular modeling studies indicated that the cross-linking data were in excellent agreement with the existence of a low-energy M3R dimer characterized by a TM5-TM5 interface. [(35)S]GTPγS binding/Gα(q/11) immunoprecipitation assays revealed that an M3R dimer that was cross-linked within the N-terminal portion of the i3 loop (264C) was functionally severely impaired (∼50% reduction in receptor-G-protein coupling, as compared to control M3R). These data support the novel concept that agonist-induced activation of M3R dimers requires a conformational change of the N-terminal segment of the i3 loop. Given the high degree of structural homology among family A GPCRs, these findings should be of broad significance.
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