G protein-coupled receptors (GPCRs): advances in structures, mechanisms, and drug discovery

Eichel, K. & von Zastrow, M. Subcellular organization of GPCR signaling. Trends Pharmacol. Sci. 39, 200–208 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rosenbaum, D. M., Rasmussen, S. G. F. & Kobilka, B. K. The structure and function of G-protein-coupled receptors. Nature 459, 356–363 (2009).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Katritch, V., Cherezov, V. & Stevens, R. C. Diversity and modularity of G protein-coupled receptor structures. Trends Pharmacol. Sci. 33, 17–27 (2012).

Article  CAS  PubMed  Google Scholar 

Latorraca, N. R., Venkatakrishnan, A. J. & Dror, R. O. GPCR dynamics: structures in motion. Chem. Rev. 117, 139–155 (2017).

Article  CAS  PubMed  Google Scholar 

Mannes, M., Martin, C., Menet, C. & Ballet, S. Wandering beyond small molecules: peptides as allosteric protein modulators. Trends Pharmacol. Sci. 43, 406–423 (2022).

Article  CAS  PubMed  Google Scholar 

Nussinov, R. Introduction to protein ensembles and allostery. Chem. Rev. 116, 6263–6266 (2016).

Article  PubMed  Google Scholar 

Dunn, H. A., Orlandi, C. & Martemyanov, K. A. Beyond the ligand: extracellular and transcellular g protein-coupled receptor complexes in physiology and pharmacology. Pharmacol. Rev. 71, 503–519 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zarzycka, B., Zaidi, S. A., Roth, B. L. & Katritch, V. Harnessing ion-binding sites for GPCR pharmacology. Pharmacol. Rev. 71, 571–595 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Flock, T. et al. Universal allosteric mechanism for Gα activation by GPCRs. Nature 524, 173–179 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dawaliby, R. et al. Allosteric regulation of G protein-coupled receptor activity by phospholipids. Nat. Chem. Biol. 12, 35–39 (2016).

Article  CAS  PubMed  Google Scholar 

Hilger, D., Masureel, M. & Kobilka, B. K. Structure and dynamics of GPCR signaling complexes. Nat. Struct. Mol. Biol. 25, 4–12 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dokholyan, N. V. Controlling allosteric networks in proteins. Chem. Rev. 116, 6463–6487 (2016).

Article  CAS  PubMed  Google Scholar 

Canals, M. et al. A Monod-Wyman-Changeux mechanism can explain G Protein-coupled Receptor (GPCR) allosteric modulation. J. Biol. Chem. 287, 650–659 (2012).

Article  CAS  PubMed  Google Scholar 

Hauser, A. S. et al. Trends in GPCR drug discovery: new agents, targets and indications. Nat. Rev. Drug Discov. 16, 829–842 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sriram, K. & Insel, P. A. G protein-coupled receptors as targets for approved drugs: how many targets and how many drugs? Mol. Pharmacol. 93, 251–258 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schöneberg, T. & Liebscher, I. Mutations in G protein-coupled receptors: mechanisms, pathophysiology and potential therapeutic approaches. Pharmacol. Rev. 73, 89–119 (2021).

Article  PubMed  Google Scholar 

Yang, D. H. et al. G protein-coupled receptors: structure- and function-based drug discovery. Signal Transduct. Target. Ther. 6, 7 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Casadó, V. & Casadó-Anguera, V. What are the current trends in G protein-coupled receptor targeted drug discovery? Expert Opin. Drug Discov. 18, 815–820 (2023).

Article  PubMed  Google Scholar 

Mohr, K. et al. Rational design of dualsteric GPCR ligands: quests and promise. Br. J. Pharmacol. 159, 997–1008 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Goupil, E., Laporte, S. A. & Hébert, T. E. Functional selectivity in GPCR signaling: understanding the full spectrum of receptor conformations. Mini Rev. Med. Chem. 12, 817–830 (2012).

Article  CAS  PubMed  Google Scholar 

Lu, S. Y., He, X. H., Ni, D. & Zhang, J. Allosteric modulator discovery: from serendipity to structure-based design. J. Med. Chem. 62, 6405–6421 (2019).

Article  CAS  PubMed  Google Scholar 

Wootten, D., Christopoulos, A. & Sexton, P. M. Emerging paradigms in GPCR allostery: implications for drug discovery. Nat. Rev. Drug Discov. 12, 630–644 (2013).

Article  CAS  PubMed  Google Scholar 

Wang, Y. et al. Allosteric binding sites at the receptor-lipid bilayer interface: novel targets for GPCR drug discovery. Drug Discov. Today 26, 690–703 (2020).

Article  PubMed  Google Scholar 

Zhang, M., Lan, X., Li, X. & Lu, S. Pharmacologically targeting intracellular allosteric sites of GPCRs for drug discovery. Drug Discov. Today 28, 103803 (2023).

Article  CAS  PubMed  Google Scholar 

Smith, R. D., Lu, J. & Carlson, H. A. Are there physicochemical differences between allosteric and competitive ligands? Plos Comput. Biol. 13, e1005813 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Slosky, L. M., Caron, M. G. & Barak, L. S. Biased allosteric modulators: new frontiers in GPCR drug discovery. Trends Pharmacol. Sci. 42, 283–299 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tan, L., Yan, W. Z., McCorvy, J. D. & Cheng, J. J. Biased ligands of G Protein-Coupled Receptors (GPCRs): Structure-Functional Selectivity Relationships (SFSRs) and therapeutic potential. J. Med. Chem. 61, 9841–9878 (2018).

Article  CAS  PubMed  Google Scholar 

Robertson, M. J., Meyerowitz, J. G. & Skiniotis, G. Drug discovery in the era of cryo-electron microscopy. Trends Biochem. Sci. 47, 124–135 (2022).

Article  CAS  PubMed  Google Scholar 

Palczewski, K. et al. Crystal structure of rhodopsin: A G protein-coupled receptor. Science 289, 739–745 (2000).

Article  CAS  PubMed  Google Scholar 

Rasmussen, S. G. F. et al. Crystal structure of the human β2 adrenergic G-protein-coupled receptor. Nature 450, 383–387 (2007).

Article  CAS  PubMed  Google Scholar 

Ghosh, E., Kumari, P., Jaiman, D. & Shukla, A. K. Methodological advances: the unsung heroes of the GPCR structural revolution. Nat. Rev. Mol. Cell Biol. 16, 69–81 (2015).

Article  CAS  PubMed  Google Scholar 

Cherezov, V. et al. High-resolution crystal structure of an engineered human β2-adrenergic G protein-coupled receptor. Science 318, 1258–1265 (2007).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rosenbaum, D. M. et al. GPCR engineering yields high-resolution structural insights into β2-adrenergic receptor function. Science 318, 1266–1273 (2007).

Article  CAS  PubMed  Google Scholar 

Chen, Q. Y. & Tesmer, J. J. G. G protein-coupled receptor interactions with arrestins and GPCR kinases: The unresolved issue of signal bias. J. Biol. Chem. 298, 102279 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li, D. F. & Caffrey, M. Structure and functional characterization of membrane integral proteins in the lipid cubic phase. J. Mol. Biol. 432, 5104–5123 (2020).

Article  CAS  PubMed  Google Scholar 

Srivastava, A. et al. High-resolution structure of the human GPR40 receptor bound to allosteric agonist TAK-875. Nature 513, 124–127 (2014).

Article  CAS  PubMed  Google Scholar 

Manglik, A., Kobilka, B. K. & Steyaert, J. Nanobodies to study G protein-coupled receptor structure and function. Annu. Rev. Pharmacol. Toxicol. 57, 19–37 (2017).

Article  CAS 

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