DOI QR코드

DOI QR Code

Structural Studies of G Protein-Coupled Receptors

  • Zhang, Dandan (CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences) ;
  • Zhao, Qiang (CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences) ;
  • Wu, Beili (CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences)
  • 투고 : 2015.10.02
  • 심사 : 2015.10.08
  • 발행 : 2015.10.31

초록

G protein-coupled receptors (GPCRs) constitute the largest and the most physiologically important membrane protein family that recognizes a variety of environmental stimuli, and are drug targets in the treatment of numerous diseases. Recent progress on GPCR structural studies shed light on molecular mechanisms of GPCR ligand recognition, activation and allosteric modulation, as well as structural basis of GPCR dimerization. In this review, we will discuss the structural features of GPCRs and structural insights of different aspects of GPCR biological functions.

키워드

참고문헌

  1. Ballesteros, J., and Weinstein, H. (1995). Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors. . Methods Neurosci. 25, 366-428. https://doi.org/10.1016/S1043-9471(05)80049-7
  2. Caffrey, M. (2011). Crystallizing membrane proteins for structurefunction studies using lipidic mesophases. Biochem. Soc. Trans. 39, 725-732. https://doi.org/10.1042/BST0390725
  3. Chae, P.S., Rasmussen, S.G., Rana, R.R., Gotfryd, K., Chandra, R., Goren, M.A., Kruse, A.C., Nurva, S., Loland, C.J., Pierre, Y., et al. (2010). Maltose-neopentyl glycol (MNG) amphiphiles for solubilization, stabilization and crystallization of membrane proteins. Nat. Methods 7, 1003-1008. https://doi.org/10.1038/nmeth.1526
  4. Cherezov, V., Rosenbaum, D.M., Hanson, M.A., Rasmussen, S.G., Thian, F.S., Kobilka, T.S., Choi, H.J., Kuhn, P., Weis, W.I., Kobilka, B.K., et al. (2007). High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science 318, 1258-1265. https://doi.org/10.1126/science.1150577
  5. Chien, E.Y., Liu, W., Zhao, Q., Katritch, V., Han, G.W., Hanson, M.A., Shi, L., Newman, A.H., Javitch, J.A., Cherezov, V., et al. (2010). Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist. Science 330, 1091-1095. https://doi.org/10.1126/science.1197410
  6. Chini, B., and Parenti, M. (2009). G-protein-coupled receptors, cholesterol and palmitoylation: facts about fats. J. Mol. Endocrinol. 42, 371-379. https://doi.org/10.1677/JME-08-0114
  7. Chrencik, J.E., Roth, C.B., Terakado, M., Kurata, H., Omi, R., Kihara, Y., Warshaviak, D., Nakade, S., Asmar-Rovira, G., Mileni, M., et al. (2015). Crystal structure of antagonist bound human lysophosphatidic Acid Receptor 1. Cell 161, 1633-1643. https://doi.org/10.1016/j.cell.2015.06.002
  8. Dore, A.S., Okrasa, K., Patel, J.C., Serrano-Vega, M., Bennett, K., Cooke, R.M., Errey, J.C., Jazayeri, A., Khan, S., Tehan, B., et al. (2014). Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane domain. Nature 511, 557-562. https://doi.org/10.1038/nature13396
  9. Fredriksson, R., Lagerstrom, M.C., Lundin, L.G., and Schioth, H.B. (2003). The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol. Pharmacol. 63, 1256-1272. https://doi.org/10.1124/mol.63.6.1256
  10. Gether, U. (2000). Uncovering molecular mechanisms involved in activation of G protein-coupled receptors. Endocr. Rev. 21, 90-113. https://doi.org/10.1210/edrv.21.1.0390
  11. Granier, S., Manglik, A., Kruse, A.C., Kobilka, T.S., Thian, F.S., Weis, W.I., and Kobilka, B.K. (2012). Structure of the delta-opioid receptor bound to naltrindole. Nature 485, 400-404. https://doi.org/10.1038/nature11111
  12. Gutierrez-de-Teran, H., Massink, A., Rodriguez, D., Liu, W., Han, G.W., Joseph, J.S., Katritch, I., Heitman, L.H., Xia, L., Ijzerman, A.P., et al. (2013). The role of a sodium ion binding site in the allosteric modulation of the A(2A) adenosine G protein-coupled receptor. Structure 21, 2175-2185. https://doi.org/10.1016/j.str.2013.09.020
  13. Haga, K., Kruse, A.C., Asada, H., Yurugi-Kobayashi, T., Shiroishi, M., Zhang, C., Weis, W.I., Okada, T., Kobilka, B.K., Haga, T., et al. (2012). Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist. Nature 482, 547-551. https://doi.org/10.1038/nature10753
  14. Hanson, M.A., Roth, C.B., Jo, E., Griffith, M.T., Scott, F.L., Reinhart, G., Desale, H., Clemons, B., Cahalan, S.M., Schuerer, S.C., et al. (2012). Crystal structure of a lipid G protein-coupled receptor. Science 335, 851-855. https://doi.org/10.1126/science.1215904
  15. Hollenstein, K., Kean, J., Bortolato, A., Cheng, R.K., Dore, A.S., Jazayeri, A., Cooke, R.M., Weir, M., and Marshall, F.H. (2013). Structure of class B GPCR corticotropin-releasing factor receptor 1. Nature 499, 438-443. https://doi.org/10.1038/nature12357
  16. Huang, J., Chen, S., Zhang, J.J., and Huang, X.Y. (2013). Crystal structure of oligomeric beta1-adrenergic G protein-coupled receptors in ligand-free basal state. Nat. Struct. Mol. Biol. 20, 419-425. https://doi.org/10.1038/nsmb.2504
  17. Huang, W.J., Manglik, A., Venkatakrishnan, A.J., Laeremans, T., Feinberg, E.N., Sanborn, A.L., Kato, H.E., Livingston, K.E., Thorsen, T.S., Kling, R.C., et al. (2015). Structural insights into mu-opioid receptor activation. Nature 524, 315-321. https://doi.org/10.1038/nature14886
  18. Jaakola, V.P., Griffith, M.T., Hanson, M.A., Cherezov, V., Chien, E.Y., Lane, J.R., Ijzerman, A.P., and Stevens, R.C. (2008). The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist. Science 322, 1211-1217. https://doi.org/10.1126/science.1164772
  19. Kang, Y., Zhou, X.E., Gao, X., He, Y., Liu, W., Ishchenko, A., Barty, A., White, T.A., Yefanov, O., Han, G.W., et al. (2015). Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature 523, 561-567. https://doi.org/10.1038/nature14656
  20. Kobilka, B.K. (2007). G protein coupled receptor structure and activation. Biochim. Biophys. Acta 1768, 794-807. https://doi.org/10.1016/j.bbamem.2006.10.021
  21. Kobilka, B.K., and Deupi, X. (2007). Conformational complexity of G-protein-coupled receptors. Trends Pharmacol. Sci. 28, 397-406. https://doi.org/10.1016/j.tips.2007.06.003
  22. Kruse, A.C., Hu, J., Pan, A.C., Arlow, D.H., Rosenbaum, D.M., Rosemond, E., Green, H.F., Liu, T., Chae, P.S., Dror, R.O., et al. (2012). Structure and dynamics of the M3 muscarinic acetylcholine receptor. Nature 482, 552-556. https://doi.org/10.1038/nature10867
  23. Lebon, G., Warne, T., Edwards, P.C., Bennett, K., Langmead, C.J., Leslie, A.G., and Tate, C.G. (2011). Agonist-bound adenosine A2A receptor structures reveal common features of GPCR activation. Nature 474, 521-525. https://doi.org/10.1038/nature10136
  24. Lebon, G., Warne, T., and Tate, C.G. (2012). Agonist-bound structures of G protein-coupled receptors. Curr Opin Struct Biol 22, 482-490. https://doi.org/10.1016/j.sbi.2012.03.007
  25. Lee, S.P., O'Dowd, B.F., and George, S.R. (2003). Homo- and hetero-oligomerization of G protein-coupled receptors. Life Sci. 74, 173-180. https://doi.org/10.1016/j.lfs.2003.09.028
  26. Lohse, M.J. (2010). Dimerization in GPCR mobility and signaling. Curr. Opin. Pharmacol. 10, 53-58. https://doi.org/10.1016/j.coph.2009.10.007
  27. Manglik, A., Kruse, A.C., Kobilka, T.S., Thian, F.S., Mathiesen, J.M., Sunahara, R.K., Pardo, L., Weis, W.I., Kobilka, B.K., and Granier, S. (2012). Crystal structure of the mu-opioid receptor bound to a morphinan antagonist. Nature 485, 321-326. https://doi.org/10.1038/nature10954
  28. Milligan, G. (2009). G protein-coupled receptor hetero-dimerization: contribution to pharmacology and function. Br J. Pharmacol. 158, 5-14. https://doi.org/10.1111/j.1476-5381.2009.00169.x
  29. Nygaard, R., Frimurer, T.M., Holst, B., Rosenkilde, M.M., and Schwartz, T.W. (2009). Ligand binding and micro-switches in 7TM receptor structures. Trends Pharmacol. Sci. 30, 249-259. https://doi.org/10.1016/j.tips.2009.02.006
  30. Palczewski, K., Kumasaka, T., Hori, T., Behnke, C.A., Motoshima, H., Fox, B.A., Le Trong, I., Teller, D.C., Okada, T., Stenkamp, R.E., et al. (2000). Crystal structure of rhodopsin: A G proteincoupled receptor. Science 289, 739-745. https://doi.org/10.1126/science.289.5480.739
  31. Park, J.H., Scheerer, P., Hofmann, K.P., Choe, H.-W., and Ernst, O.P. (2008). Crystal structure of the ligand-free G-proteincoupled receptor opsin. Nature 454, 183-187. https://doi.org/10.1038/nature07063
  32. Pin, J.P., Kniazeff, J., Binet, V., Liu, J., Maurel, D., Galvez, T., Duthey, B., Havlickova, M., Blahos, J., Prezeau, L., et al. (2004). Activation mechanism of the heterodimeric GABA(B) receptor. Biochem. Pharmacol. 68, 1565-1572. https://doi.org/10.1016/j.bcp.2004.06.035
  33. Rasmussen, S.G., Choi, H.J., Rosenbaum, D.M., Kobilka, T.S., Thian, F.S., Edwards, P.C., Burghammer, M., Ratnala, V.R., Sanishvili, R., Fischetti, R.F., et al. (2007). Crystal structure of the human beta2 adrenergic G-protein-coupled receptor. Nature 450, 383-387. https://doi.org/10.1038/nature06325
  34. Rasmussen, S.G., DeVree, B.T., Zou, Y., Kruse, A.C., Chung, K.Y., Kobilka, T.S., Thian, F.S., Chae, P.S., Pardon, E., Calinski, D., et al. (2011). Crystal structure of the beta2 adrenergic receptor-Gs protein complex. Nature 477, 549-555. https://doi.org/10.1038/nature10361
  35. Rosenbaum, D.M., Cherezov, V., Hanson, M.A., Rasmussen, S.G., Thian, F.S., Kobilka, T.S., Choi, H.J., Yao, X.J., Weis, W.I., Stevens, R.C., et al. (2007). GPCR engineering yields highresolution structural insights into beta2-adrenergic receptor function. Science 318, 1266-1273. https://doi.org/10.1126/science.1150609
  36. Rosenbaum, D.M., Zhang, C., Lyons, J.A., Holl, R., Aragao, D., Arlow, D.H., Rasmussen, S.G.F., Choi, H.-J., DeVree, B.T., Sunahara, R.K., et al. (2011). Structure and function of an irreversible agonist-${\beta}2$ adrenoceptor complex. Nature 469, 236-240. https://doi.org/10.1038/nature09665
  37. Scheerer, P., Park, J.H., Hildebrand, P.W., Kim, Y.J., Krauss, N., Choe, H.W., Hofmann, K.P., and Ernst, O.P. (2008). Crystal structure of opsin in its G-protein-interacting conformation. Nature 455, 497-502. https://doi.org/10.1038/nature07330
  38. Schlyer, S., and Horuk, R. (2006). I want a new drug: G-proteincoupled receptors in drug development. Drug Discov. Today 11, 481-493. https://doi.org/10.1016/j.drudis.2006.04.008
  39. Shimamura, T., Shiroishi, M., Weyand, S., Tsujimoto, H., Winter, G., Katritch, V., Abagyan, R., Cherezov, V., Liu, W., Han, G.W., et al. (2011). Structure of the human histamine H1 receptor complex with doxepin. Nature 475, 65-70. https://doi.org/10.1038/nature10236
  40. Siu, F.Y., He, M., de Graaf, C., Han, G.W., Yang, D., Zhang, Z., Zhou, C., Xu, Q., Wacker, D., Joseph, J.S., et al. (2013). Structure of the human glucagon class B G-protein-coupled receptor. Nature 499, 444-449. https://doi.org/10.1038/nature12393
  41. Srivastava, A., Yano, J., Hirozane, Y., Kefala, G., Gruswitz, F., Snell, G., Lane, W., Ivetac, A., Aertgeerts, K., Nguyen, J., et al. (2014). High-resolution structure of the human GPR40 receptor bound to allosteric agonist TAK-875. Nature 513, 124-127. https://doi.org/10.1038/nature13494
  42. Szczepek, M., Beyriere, F., Hofmann, K.P., Elgeti, M., Kazmin, R., Rose, A., Bartl, F.J., von Stetten, D., Heck, M., Sommer, M.E., et al. (2014). Crystal structure of a common GPCR-binding interface for G protein and arrestin. Nat. Commun. 5, 4801. https://doi.org/10.1038/ncomms5801
  43. Tan, Q., Zhu, Y., Li, J., Chen, Z., Han, G.W., Kufareva, I., Li, T., Ma, L., Fenalti, G., Li, J., et al. (2013). Structure of the CCR5 chemokine receptor-HIV entry inhibitor maraviroc complex. Science 341, 1387-1390. https://doi.org/10.1126/science.1241475
  44. Thompson, A.A., Liu, W., Chun, E., Katritch, V., Wu, H., Vardy, E., Huang, X.P., Trapella, C., Guerrini, R., Calo, G., et al. (2012). Structure of the nociceptin/orphanin FQ receptor in complex with a peptide mimetic. Nature 485, 395-399. https://doi.org/10.1038/nature11085
  45. Thomsen, W., Frazer, J., and Unett, D. (2005). Functional assays for screening GPCR targets. Curr. Opin. Biotechnol. 16, 655-665.
  46. Wacker, D., Wang, C., Katritch, V., Han, G.W., Huang, X.P., Vardy, E., McCorvy, J.D., Jiang, Y., Chu, M.H., Siu, F.Y., et al. (2013). Structural features for functional selectivity at serotonin receptors. Science 340, 615-619. https://doi.org/10.1126/science.1232808
  47. Wang, C., Jiang, Y., Ma, J., Wu, H., Wacker, D., Katritch, V., Han, G.W., Liu, W., Huang, X.P., Vardy, E., et al. (2013a). Structural basis for molecular recognition at serotonin receptors. Science 340, 610-614. https://doi.org/10.1126/science.1232807
  48. Wang, C., Wu, H., Katritch, V., Han, G.W., Huang, X.P., Liu, W., Siu, F.Y., Roth, B.L., Cherezov, V., and Stevens, R.C. (2013b). Structure of the human smoothened receptor bound to an antitumour agent. Nature 497, 338-343. https://doi.org/10.1038/nature12167
  49. Wang, C., Wu, H., Evron, T., Vardy, E., Han, G.W., Huang, X.P., Hufeisen, S.J., Mangano, T.J., Urban, D.J., Katritch, V., et al. (2014). Structural basis for Smoothened receptor modulation and chemoresistance to anticancer drugs. Nat. Commun. 5, 4355.
  50. Warne, T., Edwards, P.C., Leslie, A.G., and Tate, C.G. (2012). Crystal structures of a stabilized beta1-adrenoceptor bound to the biased agonists bucindolol and carvedilol. Structure 20, 841-849. https://doi.org/10.1016/j.str.2012.03.014
  51. White, J.F., Noinaj, N., Shibata, Y., Love, J., Kloss, B., Xu, F., Gvozdenovic-Jeremic, J., Shah, P., Shiloach, J., Tate, C.G., et al. (2012). Structure of the agonist-bound neurotensin receptor. Nature 490, 508-513. https://doi.org/10.1038/nature11558
  52. Wu, B., Chien, E.Y., Mol, C.D., Fenalti, G., Liu, W., Katritch, V., Abagyan, R., Brooun, A., Wells, P., Bi, F.C., et al. (2010). Structures of the CXCR4 Chemokine GPCR with Small- Molecule and Cyclic Peptide Antagonists. Science 330, 1066-1071. https://doi.org/10.1126/science.1194396
  53. Wu, H., Wacker, D., Mileni, M., Katritch, V., Han, G.W., Vardy, E., Liu, W., Thompson, A.A., Huang, X.P., Carroll, F.I., et al. (2012). Structure of the human kappa-opioid receptor in complex with JDTic. Nature 485, 327-332. https://doi.org/10.1038/nature10939
  54. Wu, H., Wang, C., Gregory, K.J., Han, G.W., Cho, H.P., Xia, Y., Niswender, C.M., Katritch, V., Meiler, J., Cherezov, V., et al. (2014). Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator. Science 344, 58-64. https://doi.org/10.1126/science.1249489
  55. Xu, F., Wu, H., Katritch, V., Han, G.W., Jacobson, K.A., Gao, Z.G., Cherezov, V., and Stevens, R.C. (2011). Structure of an agonistbound human A2A adenosine receptor. Science 332, 322-327. https://doi.org/10.1126/science.1202793
  56. Yin, J., Mobarec, J.C., Kolb, P., and Rosenbaum, D.M. (2015). Crystal structure of the human OX2 orexin receptor bound to the insomnia drug suvorexant. Nature 519, 247-250. https://doi.org/10.1038/nature14035
  57. Zhang, Y., DeVries, M.E., and Skolnick, J. (2006). Structure modeling of all identified G protein-coupled receptors in the human genome. Plos Comput. Biol. 2, 88-99. https://doi.org/10.1371/journal.pcbi.0020088
  58. Zhang, C., Srinivasan, Y., Arlow, D.H., Fung, J.J., Palmer, D., Zheng, Y., Green, H.F., Pandey, A., Dror, R.O., Shaw, D.E., et al. (2012). High-resolution crystal structure of human protease-activated receptor 1. Nature 492, 387-392. https://doi.org/10.1038/nature11701
  59. Zhang, J., Zhang, K., Gao, Z.G., Paoletta, S., Zhang, D., Han, G.W., Li, T., Ma, L., Zhang, W., Muller, C.E., et al. (2014a). Agonistbound structure of the human P2Y12 receptor. Nature 509, 119-122. https://doi.org/10.1038/nature13288
  60. Zhang, K., Zhang, J., Gao, Z.G., Zhang, D., Zhu, L., Han, G.W., Moss, S.M., Paoletta, S., Kiselev, E., Lu, W., et al. (2014b). Structure of the human P2Y12 receptor in complex with an antithrombotic drug. Nature 509, 115-118. https://doi.org/10.1038/nature13083
  61. Zhang, D., Gao, Z.G., Zhang, K., Kiselev, E., Crane, S., Wang, J., Paoletta, S., Yi, C., Ma, L., Zhang, W., et al. (2015a). Two disparate ligand-binding sites in the human P2Y1 receptor. Nature 520, 317-321. https://doi.org/10.1038/nature14287
  62. Zhang, H., Unal, H., Gati, C., Han, G.W., Liu, W., Zatsepin, N.A., James, D., Wang, D., Nelson, G., Weierstall, U., et al. (2015b). Structure of the Angiotensin receptor revealed by serial femtosecond crystallography. Cell 161, 833-844. https://doi.org/10.1016/j.cell.2015.04.011

피인용 문헌

  1. Recent Advances in Structure-Based Drug Design Targeting Class A G Protein-Coupled Receptors Utilizing Crystal Structures and Computational Simulations 2017, https://doi.org/10.1021/acs.jmedchem.6b01453
  2. Leveraging allostery to improve G protein-coupled receptor (GPCR)-directed therapeutics: cannabinoid receptor 1 as discovery target vol.11, pp.12, 2016, https://doi.org/10.1080/17460441.2016.1245289
  3. The impact of RGS and other G-protein regulatory proteins on Gαi-mediated signaling in immunity vol.114, 2016, https://doi.org/10.1016/j.bcp.2016.04.005
  4. Production of G protein-coupled receptors in an insect-based cell-free system vol.114, pp.10, 2017, https://doi.org/10.1002/bit.26346
  5. Drug Binding Poses Relate Structure with Efficacy in the μ Opioid Receptor vol.429, pp.12, 2017, https://doi.org/10.1016/j.jmb.2017.05.009
  6. Dynamic roles for the N-terminus of the yeast G protein-coupled receptor Ste2p vol.1859, pp.10, 2017, https://doi.org/10.1016/j.bbamem.2017.07.014
  7. Membrane-spanning α-helical barrels as tractable protein-design targets vol.372, pp.1726, 2017, https://doi.org/10.1098/rstb.2016.0213
  8. Common evolutionary binding mode of rhodopsin-like GPCRs: Insights from structural bioinformatics vol.4, pp.4, 2017, https://doi.org/10.3934/biophy.2017.4.543
  9. Receptor antagonism/agonism can be uncoupled from pharmacoperone activity vol.434, 2016, https://doi.org/10.1016/j.mce.2016.07.003
  10. Evidence of Alternative Splicing as a Regulatory Mechanism for Kissr2 in Pejerrey Fish vol.9, pp.1664-2392, 2018, https://doi.org/10.3389/fendo.2018.00604
  11. GPRC5A: An Emerging Biomarker in Human Cancer vol.2018, pp.2314-6141, 2018, https://doi.org/10.1155/2018/1823726
  12. Serial Femtosecond Crystallography of G Protein–Coupled Receptors vol.47, pp.1, 2018, https://doi.org/10.1146/annurev-biophys-070317-033239
  13. Comprehensive Analysis of Non-Synonymous Natural Variants of G Protein-Coupled Receptors vol.26, pp.2, 2018, https://doi.org/10.4062/biomolther.2017.073
  14. 최적의 luminescence 신호 분석을 위한 유전자 전달 방법의 비교연구 vol.17, pp.11, 2015, https://doi.org/10.5762/kais.2016.17.11.640
  15. Phase-plate cryo-EM structure of a class B GPCR-G protein complex vol.546, pp.7656, 2015, https://doi.org/10.1038/nature22327
  16. Functional autoantibodies directed against cell surface receptors in systemic sclerosis vol.2, pp.3, 2015, https://doi.org/10.5301/jsrd.5000241
  17. Gonadotropin-releasing hormone analog therapeutics vol.70, pp.5, 2015, https://doi.org/10.23736/s0026-4784.18.04316-2
  18. Family C G-Protein-Coupled Receptors in Alzheimer’s Disease and Therapeutic Implications vol.10, pp.None, 2019, https://doi.org/10.3389/fphar.2019.01282
  19. Small Molecule Allosteric Modulators of G-Protein-Coupled Receptors: Drug-Target Interactions vol.62, pp.1, 2019, https://doi.org/10.1021/acs.jmedchem.7b01844
  20. Characterization of Lipid-Protein Interactions and Lipid-Mediated Modulation of Membrane Protein Function through Molecular Simulation vol.119, pp.9, 2019, https://doi.org/10.1021/acs.chemrev.8b00608
  21. Recent Advances in the Drug Discovery and Development of Dualsteric/ Bitopic Activators of G Protein-Coupled Receptors vol.19, pp.26, 2019, https://doi.org/10.2174/1568026619666191009164609
  22. Elucidating the active δ-opioid receptor crystal structure with peptide and small-molecule agonists vol.5, pp.11, 2015, https://doi.org/10.1126/sciadv.aax9115
  23. Association between cannabis and the eyelids: A comprehensive review vol.48, pp.2, 2015, https://doi.org/10.1111/ceo.13687
  24. Neutrophil Signaling That Challenges Dogmata of G Protein-Coupled Receptor Regulated Functions vol.3, pp.2, 2015, https://doi.org/10.1021/acsptsci.0c00004
  25. Computational Investigations on the Binding Mode of Ligands for the Cannabinoid-Activated G Protein-Coupled Receptor GPR18 vol.10, pp.5, 2015, https://doi.org/10.3390/biom10050686
  26. GDP Release from the Open Conformation of Gα Requires Allosteric Signaling from the Agonist-Bound Human β2 Adrenergic Receptor vol.60, pp.8, 2020, https://doi.org/10.1021/acs.jcim.0c00432
  27. Establishing a sensitive fluorescence-based quantification method for cyclic nucleotides vol.20, pp.1, 2015, https://doi.org/10.1186/s12896-020-00633-y
  28. Ligand Docking Methods to Recognize Allosteric Inhibitors for G-Protein-Coupled Receptors vol.15, pp.None, 2015, https://doi.org/10.1177/11779322211037769
  29. Engineering an Allosteric Control of Protein Function vol.125, pp.7, 2015, https://doi.org/10.1021/acs.jpcb.0c11640
  30. A peptide of the N terminus of GRK5 attenuates pressure-overload hypertrophy and heart failure vol.14, pp.676, 2015, https://doi.org/10.1126/scisignal.abb5968
  31. Polyphenols and Visual Health: Potential Effects on Degenerative Retinal Diseases vol.26, pp.11, 2015, https://doi.org/10.3390/molecules26113407
  32. The human GPCR signal transduction network vol.10, pp.1, 2015, https://doi.org/10.1007/s13721-020-00278-z