In this Special Issue, The FEBS Journal highlights the important roles of G protein-coupled receptors (GPCRs) in cell physiology through fourteen Review Articles, a Viewpoint and a Structural Snapshot. GPCRs comprise the most abundant group of human cell surface receptors and perform key roles in diverse physiological processes. They have, therefore, emerged as attractive drug targets in human disease. Given the direct link between a protein’s structure and its function, the structural characterisation of GPCRs is considered of immense significance to shed light on their functional roles in the signalling pathways in which they are involved. In this editorial, Guest Editor of the Special Issue Arun Shukla reviews the latest advances in the field of activation, regulation and signalling of GPCRs as presented in this special series of articles, and we encourage you to refer to the editorial for an overview of the issue.

The articles included in this Issue emphasise how broadening our knowledge of the structure of GPCRs has aided the understanding of their activation and downstream signalling, which in turn supports the development of drugs targeting GPCRs in a specific and efficient manner.

We hope that experts and newcomers to the field alike will find these reviews timely and interesting. Many thanks go to all the authors for their remarkable contributions to this Special Issue on GPCRs.

References:

1. Shukla AK, Emerging paradigms in activation, signaling and regulation of G protein-coupled receptors, FEBS J, 2021, https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.15839
2. Hilger D, The role of structural dynamics in GPCR mediated signaling, FEBS J, 2021, https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.15841
3. Chung YK and Wong YH, Re‐examining the ‘Dissociation Model’ of G protein activation from the perspective of Gβγ signaling, FEBS J, 2021, https://doi.org/10.1111/febs.15605
4. Ma N, Nivedha AK and Vaidehi N, Allosteric Communication Regulates Ligand Specific GPCR Activity, FEBS J, 2021, https://doi.org/10.1111/febs.15826
5. Bock A and Bermudez M, Allosteric coupling and biased agonism in G protein-coupled receptors, FEBS J, 2021, https://doi.org/10.1111/febs.15783
6. Aydin Y and Coin I, Biochemical Insights into Structure and Function of Arrestins, FEBS J, 2021, https://doi.org/10.1111/febs.15811
7. Smith JS and Pack TF, Noncanonical interactions of G proteins and β-arrestins: from competitors to companions, FEBS J, 2021, https://doi.org/10.1111/febs.15749
8. Nguyen AH and Lefkowitz RJ, Signaling at the endosome: cryo-EM structure of a GPCR–G protein–βarr megacomplex, FEBS J, 2021, https://doi.org/10.1111/febs.15773
9. Bondar A and Lazar J, Optical sensors of G protein signaling, FEBS J, 2021, https://doi.org/10.1111/febs.15655
10. Soave M, Stoddart LA, White CW, Kilpatrick LE, Goulding J, Briddon SJ and Hill SJ, Detection of Genome-Edited and Endogenously Expressed G Protein-Coupled Receptors, FEBS J, 2021, https://doi.org/10.1111/febs.15729
11. Tiwari P, Fanibunda SE, Kapri D, Vasaya S, Pati S and Vaidya VA, GPCR signaling: Role in mediating the effects of early adversity in psychiatric disorders, FEBS J, 2021, https://doi.org/10.1111/febs.15738
12. Barella LF, Jain S, Kimura T and Pydi SP, Metabolic roles of G protein-coupled receptor signaling in obesity and type 2 diabetes, FEBS J, 2021, https://doi.org/10.1111/febs.15800
13. Lymperopoulos A, Cora N, Maning J, Brill AR and Sizova A, Signalling and function of cardiac autonomic nervous system receptors: Insights from the GPCR signalling universe, FEBS J, 2021, https://doi.org/10.1111/febs.15771
14. Smith NJ, Grant JN, Moon JI, So SS and Finch AM, Critically evaluating sweet taste receptor expression and signaling through a molecular pharmacology lens, FEBS J, 2021, https://doi.org/10.1111/febs.15768
15. Banerjee AA, Joseph S and Mahale SD, From cell surface to signalling and back: the life of the mammalian FSH receptor, FEBS J, 2021, https://doi.org/10.1111/febs.15649
16. Chandrabalan A and Ramachandran R, Molecular mechanisms regulating Proteinase Activated Receptors (PARs) , FEBS J, 2021, https://doi.org/10.1111/febs.15829
17. Iyison NB, Shahraki A, Kahveci K, Düzgün MB and Gün G, Are Insect GPCRs Ideal Next-Generation Pesticides: Opportunities and Challenges, FEBS J, 2021, https://doi.org/10.1111/febs.15708