1. Smit, M. J. et al. Pharmacogenomic and Structural Analysis of Constitutive G Protein–Coupled Receptor Activity. Annual Review of Pharmacology and Toxicology 47, 53–87 (2007).
2. Hauser, A. S., Attwood, M. M., Rask-Andersen, M., Schiöth, H. B. & Gloriam, D. E. Trends in GPCR drug discovery: new agents, targets and indications. Nature Reviews Drug Discovery 16, 829–842 (2017).
3. Ishihara, T. et al. Molecular cloning and expression of a cDNA encoding the secretin receptor. The EMBO Journal 10, 1635–1641 (1991).
4. Pin, J.-P. et al. The activation mechanism of class-C G-protein coupled receptors. Biology of the Cell 96, 335–342 (2004).
5. Chan, S. D. et al. Two homologs of the Drosophila polarity gene frizzled (fz) are widely expressed in mammalian tissues. Journal of Biological Chemistry 267, 25202–25207 (1992).
6. Kruse, A. C. et al. Activation and allosteric modulation of a muscarinic acetylcholine receptor. Nature 504, 101–106 (2013).
7. Xing, C. et al. Cryo-EM Structure of the Human Cannabinoid Receptor CB2-Gi Signaling Complex. Cell 180, 645-654.e13 (2020).
8. Krishna Kumar, K. et al. Structure of a signaling cannabinoid receptor 1-G protein complex. Cell 1–11 (2019) doi:10.1016/J.CELL.2018.11.040.
9. Scheer, A., Fanelli, F., Costa, T., de Benedetti, P. G. & Cotecchia, S. Constitutively active mutants of the α(1B)-adrenergic receptor: Role of highly conserved polar amino acids in receptor activation. EMBO Journal 15, 3566–3578 (1996).
10. Kim, J. M. et al. Structural origins of constitutive activation in rhodopsin: Role of the K296/E113 salt bridge. Proc Natl Acad Sci U S A 101, 12508–12513 (2004).
11. Ragnarsson, L., Andersson, Å., Thomas, W. G. & Lewis, R. J. Mutations in the NPxxY motif stabilize pharmacologically distinct conformational states of the α 1B - and β 2 -adrenoceptors. Science Signaling 12, (2019).
12. Oldham, W. M. & Hamm, H. E. Heterotrimeric G protein activation by G-protein- coupled receptors. Nature Reviews Molecular Cell Biology 9, 60–71 (2008).
13. Hurowitz, E. H. et al. Genomic Characterization of the Human Heterotrimeric G Protein α, β, and γ Subunit Genes. DNA Research 7, 111–120 (2000).
14. Milligan, G. & Kostenis, E. Heterotrimeric G-proteins: A short history. British Journal of Pharmacology 147, (2006).
15. J, L. M., L, B. J., Juan, C., G, C. M. & J, L. R. β-Arrestin: a Protein that Regulates β-adrenergic Receptor Function. Science (1979) 248, 1547–1550 (1990).
16. Hilger, D. The role of structural dynamics in GPCR-mediated signaling. The FEBS Journal 288, 2461–2489 (2021).
17. Hoeppner, C. Z., Cheng, N. & Ye, R. D. Identification of a nuclear localization sequence in β-arrestin-1 and its functional implications. J Biol Chem 287, 8932– 8943 (2012).
18. Nehmea, R. et al. Mini-G proteins: Novel tools for studying GPCRs in their active conformation. PLoS ONE 12, 1–26 (2017).
19. Ching-Ju, T. et al. Crystal structure of rhodopsin in complex with a mini-Go sheds light on the principles of G protein selectivity. Science Advances 4, eaat7052 (2022).
20. Liang, Y.-L. et al. Dominant negative G proteins enhance formation and purification of agonist-GPCR-G protein complexes for structure determination. ACS Pharmacology & Translational Science 1, 12–20 (2018).
21. Liu, P. et al. The structural basis of the dominant negative phenotype of the Gαi1β1γ2 G203A/A326S heterotrimer. Acta Pharmacologica Sinica 37, 1259–1272 (2016).
22. Rasmussen, S. G. F. et al. Crystal structure of the β2 adrenergic receptor–Gs protein complex. Nature 477, 549–555 (2011).
23. Maeda, S. et al. Development of an antibody fragment that stabilizes GPCR/G- protein complexes. Nature Communications 9, 1–9 (2018).
24. Nojima, S. et al. Cryo-EM Structure of the Prostaglandin E Receptor EP4 Coupled to G Protein. Structure 29, 252-260.e6 (2021).
25. Okamoto, H. H. et al. Cryo-EM structure of the human MT1–Gi signaling complex. Nature Structural and Molecular Biology 28, 694–701 (2021).
26. Du, Y. et al. Assembly of a GPCR-G Protein Complex. Cell 177, 1232-1242.e11 (2019).
27. Liu, X. et al. Structural Insights into the Process of GPCR-G Protein Complex Formation. Cell 177, 1243-1251.e12 (2019).
28. Young, D., Waitches, G., Birchmeier, C., Fasano, O. & Wigler, M. Isolation and characterization of a new cellular oncogene encoding a protein with multiple potential transmembrane domains. Cell 45, 711–719 (1986).
29. Lembo, P. M. C. et al. Proenkephalin A gene products activate a new family of sensory neuron-specific GPCRs. Nature Neuroscience 5, 201–209 (2002).
30. Dong, X., Han, S. kyou, Zylka, M. J., Simon, M. I. & Anderson, D. J. A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons. Cell 106, 619–632 (2001).
31. Bader, M., Alenina, N., Andrade-Navarro, M. A. & Santos, R. A. Mas and its related G protein–coupled receptors, Mrgprs. Pharmacological Reviews 66, 1080– 1105 (2014).
32. Solinski, H. J., Gudermann, T. & Breit, A. Pharmacology and signaling of MAS- related G protein–coupled receptors. Pharmacological Reviews 66, 570 LP – 597 (2014).
33. Lee, M.-G. et al. Agonists of the Mas -related Gene (Mrgs) orphan receptors as novel mediators of mast cell-censory nerve interactions. The Journal of Immunology 180, 2251–2255 (2008).
34. Steele, H. R. & Han, L. The signaling pathway and polymorphisms of Mrgprs. Neuroscience Letters 744, 135562 (2021).
35. Karhu, T. et al. Isolation of new ligands for orphan receptor MRGPRX1— hemorphins LVV-H7 and VV-H7. Peptides (N.Y.) 96, 61–66 (2017).
36. Shinohara, T. et al. Identification of a G protein-coupled peceptor specifically responsive to β-alanine*. 279, 23559–23564 (2004).
37. Zhu, P., Verma, A., Prasad, T. & Li, Q. Expression and function of Mas-related G Protein-coupled receptor D and Its ligand alamandine in retina. Molecular Neurobiology 57, 513–527 (2020).
38. Schleifenbaum, J. Alamandine and its receptor mrgd pair up to join the protective arm of the renin-angiotensin system. Frontiers in Medicine 6, 1–6 (2019).
39. Liu, Q. et al. Mechanisms of itch evoked by β-alanine. Journal of Neuroscience 32, 14532–14537 (2012).
40. Crozier, R. A., Ajit, S. K., Kaftan, E. J. & Pausch, M. H. MrgD activation inhibits KCNQ/M-currents and contributes to enhanced neuronal excitability. Journal of Neuroscience 27, 4492–4496 (2007).
41. Wang, C. et al. Facilitation of MrgprD by TRP-A1 promotes neuropathic pain. FASEB Journal 33, 1360–1373 (2019).
42. Tereza, B. et al. 5-oxoETE triggers nociception in constipation-predominant irritable bowel syndrome through MAS-related G protein–coupled receptor D. Science Signaling 11, eaal2171 (2018).
43. Soares, E. R., Barbosa, C. M., Campagnole-Santos, M. J., Santos, R. A. S. & Alzamora, A. C. Hypotensive effect induced by microinjection of Alamandine, a derivative of angiotensin-(1–7), into caudal ventrolateral medulla of 2K1C hypertensive rats. Peptides (N.Y.) 96, 67–75 (2017).
44. Coutinho, D. C. O. et al. Cardiovascular effects of angiotensin A: A novel peptide of the renin-angiotensin system. J. Renin-Angiotensin-Aldosterone Syst 15, 480–486 (2014).
45. Povlsen, A., Grimm, D., Wehland, M., Infanger, M. & Krüger, M. The vasoactive Mas receptor in essential hypertension. Journal of Clinical Medicine 9, 267 (2020).
46. Hrenak, J., Paulis, L. & Simko, F. Angiotensin A/Alamandine/MrgD axis: Another clue to understanding cardiovascular pathophysiology. International Journal of Molecular Sciences 17, (2016).
47. Guedes de Jesus, I. C. et al. Alamandine acts via MrgD to induce AMPK/NO activation against ANG II hypertrophy in cardiomyocytes. American Journal of Physiology - Cell Physiology 314, C702–C711 (2018).
48. Oliveira, A. C. et al. Genetic deletion of the alamandine receptor mrgd leads to dilated cardiomyopathy in mice. American Journal of Physiology - Heart and Circulatory Physiology 316, H123–H133 (2019).
49. Uno, M. et al. Identification of physiologically active substances as novel ligands for MRGPRD. Journal of Biomedicine and Biotechnology 2012, (2012).
50. Ajit, S. K., Pausch, M. H., Kennedy, J. D. & Kaftan, E. J. Development of a FLIPR assay for the simultaneous identification of MrgD agonists and antagonists from a single screen. Journal of Biomedicine and Biotechnology 2010, (2010).
51. Arora, R. et al. Constitutive , Basal , and β -alanine-mediated activation of the human mas-related G protein-xoupled receptor D induces release of the inflammatory cytokine IL-6 and is dependent on NF- κ B signaling. (2021).
52. Wallace, A. C., Laskowski, R. A. & Thornton, J. M. LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Engineering, Design and Selection 8, 127–134 (1995).
53. Kato, H. E. et al. Conformational transitions of a neurotensin receptor 1– Gi1 complex. Nature (2019) doi:10.1038/s41586-019-1337-6.
54. Xu, P. et al. Structures of the human dopamine D3 receptor-Gi complexes. Molecular Cell 81, 1147-1159.e4 (2021).
55. Koehl, A. et al. Structure of the μ-opioid receptor-Gi protein complex. Nature 558, 547–552 (2018).
56. Wasilko, D. J. et al. Structural basis for chemokine receptor CCR6 activation by the endogenous protein ligand CCL20. Nature Communications 11, 1–9 (2020).
57. Draper-Joyce, C. J. et al. Structure of the adenosine-bound human adenosine A1 receptor-Gi complex. Nature 558, 559–565 (2018).
58. Wheatley, M. et al. Lifting the lid on GPCRs: The role of extracellular loops. British Journal of Pharmacology 165, 1688–1703 (2012).
59. Peeters, M. C., van Westen, G. J. P., Li, Q. & Ijzerman, A. P. Importance of the extracellular loops in G protein-coupled receptors for ligand recognition and receptor activation. Trends in Pharmacological Sciences 32, 35–42 (2011).
60. Israeli, H. et al. Structure reveals the activation mechanism of the MC4 receptor to initiate satiation signaling. Science (1979) 372, 808–814 (2021).
61. Yang, F. et al. Structure, function and pharmacology of human itch receptor complexes. Nature (2021) doi:10.1038/s41586-021-04077-y.
62. Cao, C. et al. Structure, function and pharmacology of human itch GPCRs. Nature (2021) doi:10.1038/s41586-021-04126-6.
63. van Kuilenburg, A. B. P., Stroomer, A. E. M., van Lenthe, H., Abeling, N. G. G. M. & van Gennip, A. H. New insights in dihydropyrimidine dehydrogenase deficiency: A pivotal role for β-aminoisobutyric acid? Biochemical Journal 379, 119–124 (2004).
64. Tetzner, A. et al. G-Protein-coupled receptor MrgD is a receptor for angiotensin- (1-7) involving adenylyl cyclase, cAMP, and phosphokinase A. Hypertension 68, 185–194 (2016).
65. Zhang, H. et al. Structural basis for chemokine recognition and receptor activation of chemokine receptor CCR5. Nature Communications 12, 1–12 (2021).
66. Xu, P. et al. Structural insights into the lipid and ligand regulation of serotonin receptors. Nature 592, 469–473 (2021).
67. Lin, X. et al. Structural basis of ligand recognition and self-activation of orphan GPR52. Nature 579, 152–157 (2020).
68. Liu, H. et al. Structural basis of human ghrelin receptor signaling by ghrelin and the synthetic agonist ibutamoren. Nature Communications 12, 6410 (2021).
69. Scheres, S. H. W. RELION: Implementation of a Bayesian approach to cryo-EM structure determination. Journal of Structural Biology 180, 519–530 (2012).
70. Rohou, A. & Grigorieff, N. CTFFIND4: Fast and accurate defocus estimation from electron micrographs. Journal of Structural Biology 192, 216–221 (2015).
71. Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nature Methods 14, 290–296 (2017).
72. Punjani, A., Zhang, H. & Fleet, D. J. Non-uniform refinement: adaptive regularization improves single-particle cryo-EM reconstruction. Nature Methods 17, 1214–1221 (2020).
73. Pettersen, E. F. et al. UCSF Chimera - A visualization system for exploratory research and analysis. Journal of Computational Chemistry 25, 1605–1612 (2004).
74. Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallographica Section D: Biological Crystallography 66, 486–501 (2010).
75. Afonine, P. v. et al. Real-space refinement in PHENIX for cryo-EM and crystallography. Acta Crystallographica Section D: Structural Biology 74, 531– 544 (2018).
76. Inoue, A. et al. Illuminating G-Protein-Coupling Selectivity of GPCRs. Cell 177, 1933-1947.e25 (2019).
77. Lee, J. et al. CHARMM-GUI Input Generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM Simulations Using the CHARMM36 Additive Force Field. Journal of Chemical Theory and Computation 12, 405–413 (2016).
78. Jo, S., Kim, T., Iyer, V. G. & Im, W. CHARMM-GUI: A web-based graphical user interface for CHARMM. Journal of Computational Chemistry 29, 1859–1865 (2008).
79. Wu, E. L. et al. CHARMM-GUI Membrane Builder toward realistic biological membrane simulations. Journal of Computational Chemistry 35, 1997–2004 (2014).
80. Coutsias, E. A., Seok, C., Jacobson, M. P. & Dill, K. A. A kinematic view of loop closure. Journal of Computational Chemistry 25, 510–528 (2004).
81. Lomize, M. A., Pogozheva, I. D., Joo, H., Mosberg, H. I. & Lomize, A. L. OPM database and PPM web server: resources for positioning of proteins in membranes. Nucleic Acids Research 40, D370–D376 (2012).
82. Huang, J. et al. CHARMM36m: an improved force field for folded and intrinsically disordered proteins. Nature Methods 14, 71–73 (2016).
83. Vanommeslaeghe, K. et al. CHARMM general force field: A force field for drug- like molecules compatible with the CHARMM all-atom additive biological force fields. Journal of Computational Chemistry 31, 671–690 (2010).
84. Kim, S. et al. CHARMM-GUI ligand reader and modeler for CHARMM force field generation of small molecules. Journal of Computational Chemistry 38, 1879– 1886 (2017).
85. van der Spoel, D. et al. GROMACS: Fast, flexible, and free. Journal of Computational Chemistry 26, 1701–1718 (2005).
86. Hoover, W. G., Ladd, A. J. C. & Moran, B. High-Strain-Rate Plastic Flow Studied via Nonequilibrium Molecular Dynamics. Physical Review Letters 48, 1818 (1982).
87. Nosé, S. A molecular dynamics method for simulations in the canonical ensemble. Molecular Physics 52, 255–268 (1984).
88. Parrinello, M. & Rahman, A. Polymorphic transitions in single crystals: A new molecular dynamics method. Journal of Applied Physics 52, 7182 (1998).
89. Hess, B., Bekker, H., Berendsen, H. J. C. & Fraaije, J. G. E. M. LINCS: A Linear Constraint Solver for Molecular Simulations. Journal of Computational Chemistry 18, 1463–1472 (1997).
90. Hess, B. P-LINCS: A Parallel Linear Constraint Solver for Molecular Simulation. Journal of Chemical Theory and Computation 4, 116–122 (2007).
91. Darden, T., York, D. & Pedersen, L. Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems. The Journal of Chemical Physics 98, 10089 (1998).
92. Essmann, U. et al. A smooth particle mesh Ewald method. The Journal of Chemical Physics 103, 8577 (1998).
93. Michaud-Agrawal, N., Denning, E. J., Woolf, T. B. & Beckstein, O. MDAnalysis: A toolkit for the analysis of molecular dynamics simulations. Journal of Computational Chemistry 32, 2319–2327 (2011).
94. Gowers, R. J. et al. MDAnalysis: A Python Package for the Rapid Analysis of Molecular Dynamics Simulations. Proceedings of the 15th Python in Science Conference 98–105 (2016) doi:10.25080/MAJORA-629E541A-00E.
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