Molecular basis for dramatic changes in cannabinoid CB1 G protein-coupled receptor activation upon single and double point mutations

Protein Science

Volumn 22, Issue 1, 2013, Pages 101-113

  Scott, Caitlin E ^a   Abrol, Ravinder ^a   Ahn, Kwang H ^b   Kendall, Debra A ^b   Goddard, William A ^a  

^a California Institute of Technology   (United States)

^b UNIVERSITY OF CONNECTICUT   (United States)

Author keywords

Computational methods; Conformational ensemble; G protein binding; Protein structure prediction

Indexed keywords

CANNABINOID 1 RECEPTOR; GUANOSINE 5' O (3 THIOTRIPHOSPHATE);

ARTICLE; CYTOPLASM; ENZYME ACTIVITY; ENZYME BINDING; HYDROGEN BOND; PRIORITY JOURNAL; PROTEIN STRUCTURE;

HEK293 CELLS; HUMANS; MODELS, MOLECULAR; MUTANT PROTEINS; POINT MUTATION; RECEPTOR, CANNABINOID, CB1;

EID: 84873032055     PISSN: 09618368     EISSN: 1469896X     Source Type: Journal    
DOI: 10.1002/pro.2192     Document Type: Article

References (59)

1. Kenakin T, Miller LJ (2010) Seven transmembrane receptors as shapeshifting proteins: The impact of allosteric modulation and functional selectivity on new drug discovery. Pharmacol Rev 62:265-304.
2. Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M (2000) Crystal structure of rhodopsin: A G protein-coupled receptor. Science 289:739-745.
3. Okada T, Le Trong I, Fox BA, Behnke CA, Stenkamp RE, Palczewski K (2000) X-ray diffraction analysis of three-dimenrional crystals of bovine rhodopsoon obtained from mixed micelles. J Struct Biol 120:73-80.
4. Teller DC, Okada T, Behnke CA. Palczewski K. Stenkamp RE (2001) Advances in determination of a highresolution three-dimensional structure of rhodopsin, a model of G-protein-coupled receptors (GPCRs). Biochemistry 40:7761-7772.
5. Okada T, Fujiyoshi Y, Silow M, Navarro J, Landau EM, Shichida U (2002) Functional role of internal water molecules in rhodopsin revealed by x-ray crystallography. Proc Natl Acad Sci USA 99:5982-5987.
6. Okada T, Sugihara M, Bondar A-N, Elstner M, Entel P, Buss V (2004) The retinal confirmation and its in environment in rhodopsin in light of a new 2.2 A ° crystal structure. J Mol Biol 342:571-583.
7. Li J, Edwards PC, Burghammer M, Villa C, Schertler GFX (2004) Structure of bovine opsin in a trigonal crystal form. J Mol Biol 343:1409-1438.
8. Salom D, Lodowski DT, Stenkamp RE, Le Trong I, Golczak M, Jastrzebska B, Harris T, Ballesteros JA, Palczewski K (2006) Crystal structure of a photoactivated deprotonated intermediate of rhodopsin. Proc Natl Acad USA 103:16123-16128.
9. Nakamichi H, Buss V, Okada T (2007) Photoisomerization mechanism of rhodopsin and 9-cis-rhodopsin revealed by X-ray crystallography. Biophys J 92: L106-L108.
10. Standfuss JR, Xie G, Edwards PC, Burghammer M, Oprian DD, Schertler GFX (2007) Crystal structure of a thermally stable rhodopsin mutant. J Mol Biol 372: 1179-1188.
11. Stenkamp RE (2008) Alternative models for two crystal structures of bovine rhodopsin. Acta Crystallogr Sect D 64:902-904.
12. Murakami M, Kouyama T (2008) Crystal structure of squid rhodopsin. Nature 453:363-367.
13. Shimamura T, Hiraki K, Takahashi N, Hori T, Ago H, Masuda K, Takio K, Ishiguro M, Miyano, (2008) Crystal structure of squid rhodopsin with intracellularly extended cytoplasmic region. J Biol Chem 283: 17753-17756.
14. Rasmussen SGF, Choi H-J, Rosenbaum DM, Kobilka TS, Thian FS, Edwards PC, Burghammer, Ratnala VRP, Sanishvili R, Fischetti RF, Schertler GFX, Weis WI, Kobilka BK (2007) Crystal structure of the human b2 adrenergic G-protein-coupled receptor. Nature 450: 383-387.
15. Cherezov V, Rosenbaum DM, Hanson MA, Rasmussem SGF, Thian FS, Kobilka TS, Choi H-J, Kuhn P, Weis WI, Kobilka BK, Stevens RC (2007) High-resolution crystal structure of an engineered human b2-adrenergic G protein-coupled receptor. Science 318:1258-1265.
16. Hanson MA, Cherezov V, Griffith MT, Roth CB, Jaakola VP, Chien YET, Velasquez J, Kuhn P, Stevens RC (2008) A specific cholesterol binding site is established by the 2.8 A ° structure of the human b2-adrenergic receptor. Structure 16:897-905.
17. Warne T, Serrano-Vega MJ, Baker JG, Moukhametzianov R, Edwards PC, Henderson R, Leslie AGW, Tate CG, Schertler GFX (2008) Structure of a b1-adrenergic G-protein-coupled receptor. Nature 454:486-491.
18. Moukhametzianov R, Warne T, Edwards PC, Serrano- Vega MJ, Leslie AGW, Tate CG, Schertler GFX (2011) Two distinct conformations of helix 6 observed in antagonist- bound structures of a b1-adrenergic receptor. Proc Natl Acad Sci USA 108:8228-8232.
19. Jaakola V-P, Griffith MT, Hanson MA, Cherezov V, Chien EYT, Lane JR, Ijzerman AP, Stevens RC (2008) The 2.6 A ° crystal structure of a human A2A adenosine receptor bound to an antagonist. Science 322: 1211-1217.
20. Dore AS, Robertson N, Errey JC, Ng I, Hollenstein K, Tehan B, Hurrell E, Bennett K, Congreve M, Magnani F, Tate CG, Weir M, Marshall FH (2011) Structure of the adenosine A2A receptor in complex with ZM241385 and the xanthines XAC and caffeine. Structure 19: 1283-1293.
21. Chien YET, Liu W, Zhao QA, Katrich V, Han GW, Hanson MA, Shi L, Newman AH, Javitch JA, Cherezov V, Stevens RC (2010) Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist. Science 330:1091-1095.
22. Wu B, Chien EYT, Mol CD, Fenalti G, Liu W, Katritch V, Abagyan R, Brooun A, Wells P, Bi FC, Hamel DJ, Kuhn P, Handel TM, Cherezov V, Stevens RC (2010) Structures of the CXCR4 chemokine GPCR with smallmolecule and cyclic peptide antagonists. Science 330: 1066-1071.
23. Shimamura T, Shiroishi M, Weyand S, Tsujimoto H, Winter G, Katritch V, Abagyan R, Cherezov V, Liu W, Han GW, Kobayashi T, Stevens RC, Iwata S (2011) Structure of the human histamine H1 receptor complex with doxepin. Nature 475:65-70.
24. Hanson MA, Roth CB, Jo E, Griffith MT, Scott FL, Reinhart G, Desale H, Clemons B, Cahalan SM, Schuerer SC, Sana MG, Han GW, Kuhn P, Rosen H, Stevens RC (2012) Crystal structure of a lipid G protein-coupled receptor. Science 335:851-855.
25. Manglik A, Kruse AC, Kobilka TS, Thian FS, Mathiesen JM, Sunahara RK, Pardo L, Weis WI, Kobilka BK, Granier S (2012) Crystal structure of the l-opioid receptor bound to a morphinan antagonist. Nature 485: 321-326.
26. Granier S, Manglik A, Kruse AC, Kobilka TS, Thian FS, Weis WI, Kobilka BK (2012) Structure of the dopioid receptor bound to naltrindole. Nature 485: 400-404.
27. Wu H, Wacker D, Mileni M, Katritch V, Han GW, Vardy E, Liu W, Thompson AA, Huang X-P, Carroll FI, Mascarella SW, Westkaemper RB, Mosier PD, Roth BL, Cherezov V, Stevens RC (2012) Structure of the human j-opioid receptor in complex with JDTic. Nature 485: 327-332.
28. Thompson AA, Liu W, Chun E, Katritch V, Vardy E, Huang X-P, Trapella C, Guerrini R, Carlo G, Roth BL, Cherezov V, Stevens RC (2012) Structure of the nociceptin/ orphanin FQ receptor in complex with a peptide mimetic. Nature 485:395-399.
29. Park JH, Scheerer P, Hofmann KP, Choe H-W, Ernst OP (2008) Crystal structure of the ligand-free G-protein- coupled receptor opsin. Nature 454:183-187.
30. Scheerer P, Park JH, Hildebrand PW, Kim YJ, Krauss N, Choe HW, Hofmann KP, Ernst OP (2008) Crystal structure of opsin in its G-protein-interacting conformation. Nature 455:497-502.
31. Choe HW, Kim YJ, Park JH, Morizumi T, Pai EF, Krauss N, Hofmann KP, Scheerer P, Ernst OP (2011) Crystal structure of metarhodopsin II. Nature 471: 651-655.
32. Standfuss J, Edwards PCC, D'Antona A, Fransen M, Xie G, Oprian DD, Schertler GFX (2011) The structural basis of agonist-induced activation in constitutively active rhodopsin. Nature 471:656-660.
33. Rosenbaum DM, Zhang C, Lyons JA, Holl R, Aragao D, Arlow DH, Rasmussen SGF, Choi H-J, DeVree BT, Sunahara RK, Chae PS, Gellman SH, Dror RO, Shaw DE, Weis WI, Caffrey M, Gmeiner P, Kobilka BK (2011) Structure and function of an irreversible agonist- b2 adrenoceptor complex. Nature 469:236-240.
34. Rasmussen SGF, Choi H-J, Fung JJ, Pardon E, Casarosa P, Chae PS, DeVree BT, Rosenbaum DM, Thian FS, Kobilka TS, Schnapp A, Konetzki I, Sunahara RK, Gellman SH, Pautsch A, Steyaert J, Weis WI, Kobilka BK (2011) Structure of a nanobody-stabilized active state of the b2 adrenoceptor. Nature 469:175-180.
35. Rasmussen SGF, DeVree BT, Zou Y, Kruse AC, Chung KY, Kobilka TS, Thian FS, Chae PS, Pardon E, Calinski D, Mathiesen JM, Shah STA, Lyons JA, Caffrey M, Gellman SH, Steyaert J, Skiniotis G, Weis WI, Sunahara RK, Kobilka BK (2011) Crystal structure of the b2 adrenergic receptor-Gs protein complex. Nature 477: 549-555.
36. Xu F, Wu HX, Katritch V, Han GW, Jacobson KA, Gao ZG, Cherezov V, Stevens RC (2011) Structure of an agonist- bound human A2A adenosine receptor. Science 332: 322-327.
37. Lebon G, Warne T, Edwards PC, Bennett K, Langmead CJ, Leslie AGW, Tate CG (2011) Agonist-bound adenosine A2A receptor structures reveal common features of GPCR activation. Nature 474:521-525.
38. D'Antona A, Ahn KH, Kendall DA (2006) Mutations of CB1 T210 produce active and inactive receptor forms: correlations with ligand affinity, receptor stability, and cellular localization. Biochemistry 45:5606-5617.
39. Ballesteros JA, Weinstein H. Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors. In: Sealfon SC, Ed. (1995) Receptor molecular biology, Vol. 25. Academic Press: Waltham, Massachusetts, pp 366-428.
40. Abrol R, Bray JK, Goddard WA, III (2012) BiHelix: towards de novo structure prediction of an ensemble of G-protein coupled receptor conformations. Proteins Struct Funct Bioinf 80:505-518.
41. Abrol R, Griffith AR, Bray JK, Goddard WA. Structure prediction of G protein-coupled receptors and their ensemble of functionally important conformations. In: Vaidehi N, Klein-Seetharaman J, Eds. (2012) Membrane protein structure: methods and protocols, Vol. 914. Humana Press: New York, NY, pp 237-254.
42. Ballesteros JA, Jensen AD, Liapakis G, Rasmussen SGF, Shi L, Gether U, Javitch JA (2001) Activation of the b2-adrenergic receptor involves disruption of an ionic lock between the cytoplasmic ends of transmembrane segments 3 and 6. J Biol Chem 276: 29171-29177.
43. Yao XJ, Parnot C, Deupi X, Ratnala VRP, Swaminath G, Farrens D, Kobilka B (2006) Coupling ligand structure to specific conformational switches in the b2-adrenoceptor. Nat Chem Biol 2:417-422.
44. Crocker E, Eilers M, Ahuja S, Hornak V, Hirshfeld A, Sheves M, Smith SO (2006) Location of Trp265 in metarhodopsin II: implications for the activation mechanism of the visual receptor rhodopsin. J Mol Biol 357: 163-172.
45. Rhee MH, Nevo I, Levy R, Vogel Z (2000) Role of the highly conserved Asp-Arg-Tyr motif in signal transduction of the CB2 cannabinoid receptor. FEBS Lett 466: 300-304.
46. Feng WK, Song ZH (2003) Effects of D3.49A, R3.50A, and A6.34E mutations on ligand binding and activation of the cannabinoid-2 (CB2) receptor. Biochem Pharmacol 65:1077-1085.
47. Hurst DP, Lynch DL, Barnett-Norris J, Hyatt SM, Seltzman HH, Zhong M, Song ZH, Nie JJ, Lewis D, Reggio PH (2002) N-(Piperidin-1-yl)-5-(4-chlorophenyl) - 1-(2,4-dichlorophenyl)-4-methyl-1H -pyrazole-3-carboxamide (SR141716A) interaction with LYS 3.28(192) is crucial for its inverse agonism at the cannabinoid CB1 receptor. Mol Pharmacol 62:1274-1287.
48. Singh R, Hurst DP, Barnett-Norris J, Lynch DL, Reggio PH, Guarnieri F (2002) Activation of the cannabinoid CB1 receptor may involve a W6.48/F3.36 rotamer toggle switch. J Pept Res 60:357-370.
49. McAllister SD, Rizvi G, Anavi-Goffer S, Hurst DP, Barnett- Norris J, Lynch DL, Reggio PH, Abood ME (2003) An aromatic microdomain at the cannabinoid CB1 receptor constitutes an agonist/inverse agonist binding region. J Med Chem 46:5139-5152.
50. Hurst D, Umejiego U, Lynch D, Seltzman H, Hyatt S, Roche M, McAllister S, Fleischer D, Kapur A, Abood M, Shi S, Jones J, Lewis D, Reggio P (2006) Biarylpyrazole inverse agonists at the cannabinoid CB1 receptor: Importance of the C-3 carboxamide oxygen/lysine3.28 (192) interaction. J Med Chem 49:5969-5987.
51. D'Antona A, Ahn KH, Wang L, Mierke DF, Lucas- Lenard J, Kendall DA (2006) A cannabinoid receptor 1 mutation proximal to the DRY motif results in constitutive activity and reveals intramolecular interactions involved in receptor activation. Brain Res 1108:1-11.
52. Shim J-Y (2009) Transmembrane helical domain of the cannabinoid CB1 receptor. Biophys J 96:3251-3262.
53. Shim J-Y (2010) Understanding functional residues of the cannabinoid CB1 receptor for drug discovery. Curr Top Med Chem 10:779-798.
54. Fiser A, Sali A (2003) Modeller: generation and refinement of homology-based protein structure models. Methods Enzymol 374:461-491.
55. Pieper U, Webb BM, Barkan DT, Schneidman-Duhovny D, Schlessinger A, Braberg H, Yang Z, Meng EC, Pettersen EF, Huang CC, Datta RS, Sampathkumar P, Madhusudhan MS, Sjolander K, Ferrin TE, Burley SK, Sali A (2011) MODBASE, a database of annotated comparative protein structure models and associated resources. Nucleic Acids Res 39:D465-D474.
56. Ahn KH, Bertalovitz AC, Mierke DF, Kendall DA (2009) Dual role of the second extracellular loop of the cannabinoid receptor 1: ligand binding and receptor localization. Mol Pharmacol 76:833-842.
57. Mayo SL, Olafson BD, Goddard WA (1990) DREIDING: a generic force field for molecular simulations. J Phys Chem 94:8897-8909.
58. Wimley WC, Creamer TP, White SH (1996) Solvation energies of amino acid side chains and backbone in a family of host-guest pentapeptides. Biochemistry 35: 5109-5124.
59. Kam VWT, Goddard WA (2008) Flat-bottom strategy for improved accuracy in protein side-chain placements. J Chem Theory Comput 4:2160-2169.