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Glukhova A, Draper-Joyce CJ, Sunahara RK, et al. Rules of Engagement: GPCRs and G Proteins. ACS Pharmacol Transl Sci. 2018;1(2):73-83doi: 10.1021/acsptsci.8b00026.
Glukhova, A., Draper-Joyce, C. J., Sunahara, R. K., Christopoulos, A., Wootten, D., & Sexton, P. M. (2018). Rules of Engagement: GPCRs and G Proteins. ACS pharmacology & translational science, 1(2), 73-83. https://doi.org/10.1021/acsptsci.8b00026
Glukhova, Alisa, et al. "Rules of Engagement: GPCRs and G Proteins." ACS pharmacology & translational science vol. 1,2 (2018): 73-83. doi: https://doi.org/10.1021/acsptsci.8b00026
Glukhova A, Draper-Joyce CJ, Sunahara RK, Christopoulos A, Wootten D, Sexton PM. Rules of Engagement: GPCRs and G Proteins. ACS Pharmacol Transl Sci. 2018 Sep 07;1(2):73-83. doi: 10.1021/acsptsci.8b00026. eCollection 2018 Nov 09. PMID: 32219204; PMCID: PMC7089011.
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ACS Pharmacol Transl Sci. 2018 Sep 07;1(2):73-83. doi: 10.1021/acsptsci.8b00026. eCollection 2018 Nov 09.

Rules of Engagement: GPCRs and G Proteins.

ACS pharmacology & translational science

Alisa Glukhova, Christopher J Draper-Joyce, Roger K Sunahara, Arthur Christopoulos, Denise Wootten, Patrick M Sexton

Affiliations

  1. Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
  2. Department of Pharmacology, University of California San Diego School of Medicine, La Jolla, California 92093, United States.
  3. School of Pharmacy, Fudan University, Shanghai, 201203, China.

PMID: 32219204 PMCID: PMC7089011 DOI: 10.1021/acsptsci.8b00026

Abstract

G protein-coupled receptors (GPCRs) are a key drug target class. They account for over one-third of current pharmaceuticals, and both drugs that inhibit and promote receptor function are important therapeutically; in some cases, the same GPCR can be targeted with agonists and inhibitors, depending upon disease context. There have been major breakthroughs in understanding GPCR structure and drug binding through advances in X-ray crystallography, and membrane protein stabilization. Nonetheless, these structures have predominately been of inactive receptors bound to inhibitors. Efforts to capture structures of fully active GPCRs, in particular those in complex with the canonical, physiological transducer G protein, have been limited via this approach. Very recently, advances in cryo-electron microscopy have provided access to agonist:GPCR:G protein complex structures. These promise to revolutionize our understanding of GPCR:G protein engagement and provide insight into mechanisms of efficacy and coupling selectivity and how these might be controlled by biased agonists. Here we review what we have currently learned from the new GPCR:Gs and GPCR:Gi/o complex structures.

Copyright © 2018 American Chemical Society.

Conflict of interest statement

The authors declare no competing financial interest.

References

  1. Cell. 1992 Mar 6;68(5):911-22 - PubMed
  2. Nature. 2018 Mar 1;555(7694):121-125 - PubMed
  3. Nature. 2017 Jun 1;546(7656):118-123 - PubMed
  4. Nature. 2011 Jul 19;477(7366):549-55 - PubMed
  5. Protein Sci. 2018 Jan;27(1):112-128 - PubMed
  6. Nature. 2018 Jun;558(7711):620-623 - PubMed
  7. Nature. 2018 Jun;558(7711):559-563 - PubMed
  8. Science. 2015 Mar 6;347(6226):1113-7 - PubMed
  9. Mol Pharmacol. 2000 Jun;57(6):1081-92 - PubMed
  10. Nature. 2018 Sep;561(7724):492-497 - PubMed
  11. J Am Chem Soc. 2014 Aug 13;136(32):11244-7 - PubMed
  12. J Biol Chem. 1992 Jan 15;267(2):1212-8 - PubMed
  13. Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):16086-91 - PubMed
  14. Science. 2012 Jul 13;337(6091):232-6 - PubMed
  15. J Biol Chem. 1999 Mar 19;274(12):7865-9 - PubMed
  16. Nature. 2013 Jul 25;499(7459):444-9 - PubMed
  17. PLoS One. 2017 Apr 20;12(4):e0175642 - PubMed
  18. Curr Opin Struct Biol. 2016 Dec;41:247-254 - PubMed
  19. Yeast. 2000 Jan 15;16(1):11-22 - PubMed
  20. Nature. 2018 Jun;558(7711):553-558 - PubMed
  21. Elife. 2018 May 04;7: - PubMed
  22. Nucleic Acids Res. 2013 Jan;41(Database issue):D824-7 - PubMed
  23. Nature. 2011 Sep 28;477(7366):611-5 - PubMed
  24. Nature. 2012 Mar 21;485(7398):321-6 - PubMed
  25. Science. 2013 May 3;340(6132):610-4 - PubMed
  26. Biochemistry. 1993 Mar 9;32(9):2438-54 - PubMed
  27. Nature. 2015 Aug 20;524(7565):315-21 - PubMed
  28. Nature. 2016 Aug 4;536(7614):104-7 - PubMed
  29. Annu Rev Biophys. 2018 Mar 2;: - PubMed
  30. Pharmacol Ther. 2012 Jan;133(1):40-69 - PubMed
  31. Nature. 2015 Aug 13;524(7564):173-179 - PubMed
  32. Nature. 1993 May 20;363(6426):274-6 - PubMed
  33. J Biol Chem. 1993 Oct 25;268(30):22273-6 - PubMed
  34. Cell. 2017 Feb 23;168(5):867-877.e13 - PubMed
  35. Science. 2007 Nov 23;318(5854):1266-73 - PubMed
  36. J Cell Sci. 2002 Feb 1;115(Pt 3):455-65 - PubMed
  37. Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):499-504 - PubMed
  38. J Mol Biol. 2016 Sep 25;428(19):3850-68 - PubMed
  39. J Mol Biol. 2004 Sep 10;342(2):571-83 - PubMed
  40. Nature. 2015 Jul 30;523(7562):561-7 - PubMed
  41. FEBS Lett. 1999 Jan 25;443(2):205-8 - PubMed
  42. Science. 2015 Jun 19;348(6241):1361-5 - PubMed
  43. Biochim Biophys Acta. 2008 Jul-Aug;1778(7-8):1640-52 - PubMed
  44. Mol Pharmacol. 2006 Jun;69(6):1984-9 - PubMed
  45. J Mol Biol. 2012 Mar 16;417(1-2):95-111 - PubMed
  46. J Biol Chem. 2014 Aug 29;289(35):24475-87 - PubMed
  47. Nature. 2018 Jun;558(7711):547-552 - PubMed
  48. Nature. 2017 Jun 8;546(7657):248-253 - PubMed
  49. Cell. 2016 Oct 20;167(3):739-749.e11 - PubMed
  50. Nature. 2011 May 18;474(7352):521-5 - PubMed
  51. Mol Pharmacol. 2006 Nov;70(5):1750-60 - PubMed
  52. J Pharmacol Exp Ther. 2009 Oct;331(1):277-86 - PubMed
  53. Biochemistry. 2009 Jun 16;48(23):5159-70 - PubMed
  54. Science. 2014 Mar 28;343(6178):1443-4 - PubMed
  55. Protein Eng Des Sel. 2016 Dec;29(12):583-594 - PubMed
  56. J Biol Chem. 2002 Jun 7;277(23):21080-5 - PubMed
  57. Nat Chem Biol. 2016 Jan;12(1):35-9 - PubMed
  58. J Biol Chem. 2003 Dec 12;278(50):50530-6 - PubMed
  59. Curr Protein Pept Sci. 2013 Aug;14(5):407-15 - PubMed

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