Activation and allosteric modulation of a muscarinic acetylcholine receptor

Nature

Volumn 504, Issue 7478, 2013, Pages 101-106

  Kruse, Andrew C ^a   Ring, Aaron M ^a   Manglik, Aashish ^a   Hu, Jianxin ^b   Hu, Kelly ^b   Eitel, Katrin ^c   Hübner, Harald ^c   Pardon, Els ^d,e   Valant, Celine ^f   Sexton, Patrick M ^f   Christopoulos, Arthur ^f   Felder, Christian C ^g   Gmeiner, Peter ^c   Steyaert, Jan ^d,e   Weis, William I ^a   Garcia, K Christopher ^a   Wess, Jürgen ^b   Kobilka, Brian K ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

^c UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^d VRIJE UNIVERSITEIT BRUSSEL   (Belgium)

^e DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^f MONASH UNIVERSITY   (Australia)

^g ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA 2 ADRENERGIC RECEPTOR; G PROTEIN COUPLED RECEPTOR; MUSCARINIC M2 RECEPTOR; RHODOPSIN;

ANTIBODY; CHEMICAL BINDING; CRYSTALLOGRAPHY; PROTEIN; YEAST;

ALLOSTERISM; ARTICLE; ARTIODACTYLA; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; CRYSTAL STRUCTURE; CRYSTALLIZATION; HUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; VESTIBULE; YEAST;

ALLOSTERIC REGULATION; BINDING SITES; CYTOPLASM; HUMANS; MODELS, MOLECULAR; PROTEIN BINDING; PROTEIN STRUCTURE, TERTIARY; RECEPTORS, MUSCARINIC;

CAMELIDAE;

EID: 84889564886     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature12735     Document Type: Article

References (48)

1. Wess, J., Eglen, R. M. & Gautam, D. Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development. Nature Rev. Drug Discov. 6, 721-733 (2007).
2. Peterson, G. L., Herron, G. S., Yamaki, M., Fullerton, D. S. & Schimerlik, M. I. Purification of themuscarinic acetylcholine receptor from porcine atria. Proc. Natl Acad. Sci. USA 81, 4993-4997 (1984).
3. Kubo, T. et al. Primary structure of porcine cardiac muscarinic acetylcholine receptor deduced from the cDNA sequence. FEBS Lett. 209, 367-372 (1986).
4. Mohr, K., Trankle, C. & Holzgrabe, U. Structure/activity relationships of M2 muscarinic allosteric modulators. Receptors Channels 9, 229-240 (2003).
5. Digby, G. J., Shirey, J. K.&Conn, P. J. Allosteric activators ofmuscarinic receptors as novel approaches for treatment of CNS disorders. Mol. Biosyst. 6, 1345-1354 (2010).
6. Keov, P., Sexton, P. M. & Christopoulos, A. Allosteric modulation of G proteincoupled receptors: a pharmacological perspective. Neuropharmacology60, 24-35 (2011).
7. Haga, K. et al. Structure of the humanM2muscarinic acetylcholine receptor bound to an antagonist. Nature 482, 547-551 (2012).
8. Kruse, A. C. et al. Structure and dynamics of the M3 muscarinic acetylcholine receptor. Nature 482, 552-556 (2012).
9. Choe, H. W. et al. Crystal structure of metarhodopsin II. Nature 471, 651-655 (2011).
10. Rasmussen, S. G. et al. Crystal structure of the b2 adrenergic receptor-Gs protein complex. Nature 477, 549-555 (2011).
11. Rasmussen, S. G. et al. Structure of a nanobody-stabilized active state of the b2 adrenoceptor. Nature 469, 175-180 (2011).
12. Deupi, X. et al. Stabilized G protein binding site in the structure of constitutively active metarhodopsin-II. Proc. Natl Acad. Sci. USA 109, 119-124 (2012).
13. Scheerer, P. et al. Crystal structure of opsin in its G-protein-interacting conformation. Nature 455, 497-502 (2008).
14. Nygaard, R. et al. The dynamic process of b2-adrenergic receptor activation. Cell 152, 532-542 (2013).
15. Kloeckner, J., Schmitz, J. & Holzgrabe, U. Convergent, short synthesis of the muscarinic superagonist iperoxo. Tetrahedr. Lett. 51, 3470-3472 (2010).
16. Hudgins, P. M. & Stubbins, J. F. A comparison of the action of acetylcholine and acetylcholine mustard (chloroethylmethylaminoethyl acetate) on muscarinic and nicotinic receptors. J. Pharmacol. Exp. Ther. 182, 303-311 (1972).
17. Spalding, T. A., Birdsall, N. J., Curtis, C. A. & Hulme, E. C. Acetylcholine mustard labels the binding site aspartate in muscarinic acetylcholine receptors. J. Biol. Chem. 269, 4092-4097 (1994).
18. Ring, A. M. et al. Adrenaline-activated structure of the b2-adrenoceptor stabilized by an engineered nanobody. Nature 502, 575-579 (2013).
19. Miao, Y., Nichols, S. E., Gasper, P. M., Metzger, V. T. & McCammon, J. A. Activation anddynamicnetwork of theM2muscarinic receptor. Proc.Natl Acad. Sci.USA110, 10982-10987 (2013).
20. Ballesteros, J. A. et al. Activation of the b2-adrenergic receptor involves disruption of an ionic lock between the cytoplasmic ends of transmembrane segments 3 and J. Biol. Chem. 276, 29171-29177 (2001).
21. Heitz, F. et al. Site-directed mutagenesis of the putative human muscarinic M2 receptor binding site. Eur. J. Pharmacol. 380, 183-195 (1999).
22. Wess, J., Maggio, R., Palmer, J. R. & Vogel, Z. Role of conserved threonine and tyrosine residues in acetylcholine binding and muscarinic receptor activation. A study with m3 muscarinic receptor point mutants. J. Biol. Chem. 267, 19313-19319 (1992).
23. Vogel, W. K., Sheehan, D. M. & Schimerlik, M. I. Site-directed mutagenesis on the m2muscarinic acetylcholine receptor: the significance of Tyr403in the binding of agonists and functional coupling. Mol. Pharmacol. 52, 1087-1094 (1997).
24. Gregory, K. J., Hall, N. E., Tobin, A. B., Sexton, P. M.& Christopoulos, A. Identification of orthosteric and allosteric site mutations in M2 muscarinic acetylcholine receptors that contribute to ligand-selective signaling bias. J. Biol. Chem. 285, 7459-7474 (2010).
25. De Amici, M., Dallanoce, C., Holzgrabe, U., Trankle, C. & Mohr, K. Allosteric ligands for G protein-coupled receptors: a novel strategy with attractive therapeutic opportunities. Med. Res. Rev. 30, 463-549 (2010).
26. Gregory, K. J., Sexton, P. M.&Christopoulos, A. Allostericmodulation ofmuscarinic acetylcholine receptors. Curr. Neuropharmacol. 5, 157-167 (2007).
27. Bock, A. et al. The allosteric vestibule of a seven transmembrane helical receptor controls G-protein coupling. Nature Commun. 3, 1044 (2012).
28. May, L. T. et al. Structure-function studies of allosteric agonism at M2 muscarinic acetylcholine receptors. Mol. Pharmacol. 72, 463-476 (2007).
29. Valant, C., Felder, C. C., Sexton, P. M. & Christopoulos, A. Probe dependence in the allosteric modulation of a G protein-coupled receptor: implications for detection and validation of allosteric ligand effects. Mol. Pharmacol. 81, 41-52 (2012).
30. Prilla, S., Schrobang, J., Ellis, J., Holtje, H. D. & Mohr, K. Allosteric interactions with muscarinic acetylcholine receptors: complex role of the conserved tryptophan M2422Trp in a critical cluster of amino acids for baseline affinity, subtype selectivity, and cooperativity. Mol. Pharmacol. 70, 181-193 (2006).
31. Chee, M. J. et al. The third intracellular loop stabilizes the inactive state of the neuropeptide Y1 receptor. J. Biol. Chem. 283, 33337-33346 (2008).
32. Broach, J. R. & Thorner, J. High-throughput screening for drug discovery. Nature 384, 14-16 (1996).
33. Ehlert, F. J. Estimation of the affinities of allosteric ligands using radioligand binding and pharmacological nullmethods. Mol. Pharmacol. 33, 187-194 (1988).
34. Canals, M. et al. A Monod-Wyman-Changeux mechanism can explain G proteincoupled receptor (GPCR) allosteric modulation. J. Biol. Chem. 287, 650-659 (2012).
35. Leach, K., Sexton, P. M. & Christopoulos, A. Allosteric GPCR modulators: taking advantage of permissive receptor pharmacology. Trends Pharmacol. Sci. 28, 382-389 (2007).
36. Ichiyama, S. et al. The structure of the third intracellular loop of the muscarinic acetylcholine receptor M2 subtype. FEBS Lett. 580, 23-26 (2006).
37. Shapiro, R. A. & Nathanson, N. M. Deletion analysis of the mouse m1 muscarinic acetylcholine receptor: effects on phosphoinositide metabolism and downregulation. Biochemistry 28, 8946-8950 (1989).
38. Conrath, K. E. et al. b-Lactamase inhibitors derived from single-domain antibody fragments elicited in the camelidae. Antimicrob. Agents Chemother. 45, 2807-2812 (2001).
39. Whorton, M. R. et al. A monomeric G protein-coupled receptor isolated in a highdensity lipoprotein particle efficiently activates its G protein. Proc. Natl Acad. Sci. USA 104, 7682-7687 (2007).
40. Hu, J. et al. Structural basis of G protein-coupled receptor-G protein interactions. Nature Chem. Biol. 6, 541-548 (2010).
41. Liu, J., Conklin, B. R., Blin, N., Yun, J.&Wess, J. Identification of a receptor/G-protein contact site critical for signaling specificity and G-protein activation. Proc. Natl Acad. Sci. USA 92, 11642-11646 (1995).
42. Li, B. et al. Rapid identification of functionally critical amino acids in a G proteincoupled receptor. Nature Methods 4, 169-174 (2007).
43. McMillin,S.M.,Heusel,M., Liu, T.,Costanzi, S.&Wess, J.StructuralbasisofM3muscarinic receptor dimer/oligomer formation. J. Biol. Chem. 286, 28584-28598 (2011).
44. Caffrey, M. & Cherezov, V. Crystallizing membrane proteins using lipidic mesophases. Nature Protocols 4, 706-731 (2009).
45. Otwinowski, Z. & Minor, W. in Methods in Enzymology Vol. 276 (ed. Carter, C. W.) 307-326 (Academic, 1997).
46. McCoy, A. J. et al.Phaser crystallographic software. J.Appl. Crystallogr.40, 658-674 (2007).
47. Afonine, P. V. et al. Towards automated crystallographic structure refinement with phenix.refine. Acta Crystallogr. D 68, 352-367 (2012).
48. Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D 60, 2126-2132 (2004).