Allosteric binding site in a Cys-loop receptor ligand-binding domain unveiled in the crystal structure of ELIC in complex with chlorpromazine

Proceedings of the National Academy of Sciences of the United States of America

Volumn 113, Issue 43, 2016, Pages E6696-E6703

  Nys, Mieke ^a   Wijckmans, Eveline ^a   Farinha, Ana ^a   Yoluk, Özge ^b,c   Andersson, Magnus ^b,c   Brams, Marijke ^a   Spurny, Radovan ^a,f   Peigneur, Steve ^d   Tytgat, Jan ^d   Lindahl, Erik ^b,c,e   Ulens, Chris ^a  

^a LABORATORY OF MOLECULAR AND CELLULAR SIGNALING   (Belgium)

^b SCIENCE FOR LIFE LABORATORY   (Sweden)

^c ROYAL INSTITUTE OF TECHNOLOGY   (Sweden)

^d DEPARTMENT OF PHARMACEUTICAL AND PHARMACOLOGICAL SCIENCES   (Belgium)

^e STOCKHOLM UNIVERSITY   (Sweden)

^f MASARYK UNIVERSITY   (Czech Republic)

Author keywords

Allosteric modulation; Cys loop receptor; Ligand gated ion channel; Nicotinic acetylcholine receptor; X ray crystallography

Indexed keywords

CHLORPROMAZINE; CYSTEINE LOOP LIGAND GATED ION CHANNEL RECEPTOR; ERWINIA LIGAND GATED ION CHANNEL; LIGAND GATED ION CHANNEL; NEUROTRANSMITTER; UNCLASSIFIED DRUG; BACTERIAL PROTEIN; NEUROLEPTIC AGENT; PROTEIN BINDING; RECOMBINANT PROTEIN;

ALLOSTERISM; CONFERENCE PAPER; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; ELECTROPHYSIOLOGY; ERWINIA; HYDROGEN BOND; MOLECULAR DYNAMICS; NONHUMAN; PHOTOAFFINITY LABELING; PRIORITY JOURNAL; X RAY CRYSTALLOGRAPHY; ALLOSTERIC SITE; ALPHA HELIX; ANALOGS AND DERIVATIVES; ANIMAL; BETA SHEET; CHEMISTRY; CYTOLOGY; ESCHERICHIA COLI; GENE EXPRESSION; GENETICS; HALOGENATION; KINETICS; METABOLISM; MOLECULAR MODEL; OOCYTE; PROTEIN DOMAIN; XENOPUS LAEVIS;

ALLOSTERIC REGULATION; ALLOSTERIC SITE; ANIMALS; ANTIPSYCHOTIC AGENTS; BACTERIAL PROTEINS; CHLORPROMAZINE; CRYSTALLOGRAPHY, X-RAY; CYSTEINE LOOP LIGAND-GATED ION CHANNEL RECEPTORS; ERWINIA; ESCHERICHIA COLI; GENE EXPRESSION; HALOGENATION; KINETICS; MODELS, MOLECULAR; OOCYTES; PROTEIN BINDING; PROTEIN CONFORMATION, ALPHA-HELICAL; PROTEIN CONFORMATION, BETA-STRAND; PROTEIN INTERACTION DOMAINS AND MOTIFS; RECOMBINANT PROTEINS; XENOPUS LAEVIS;

EID: 84992395900     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1603101113     Document Type: Article

References (83)

1. Ban TA (2007) Fifty years chlorpromazine: A historical perspective. Neuropsychiatr Dis Treat 3(4):495-500.
2. Baumeister AA (2013) The chlorpromazine enigma. J Hist Neurosci 22(1):14-29.
3. Snyder SH, Banerjee SP, Yamamura HI, Greenberg D (1974) Drugs, neurotransmitters, and schizophrenia. Science 184(4143):1243-1253.
4. Seeman P (1980) Brain dopamine receptors. Pharmacol Rev 32(3):229-313.
5. Mathie A, Wooltorton JR, Watkins CS (1998) Voltage-activated potassium channels in mammalian neurons and their block by novel pharmacological agents. Gen Pharmacol 30(1):13-24.
6. + current in rat phaeochromocytoma cells. Br J Pharmacol 116(6):2603-2610.
7. Dinan TG, Crunelli V, Kelly JS (1987) Neuroleptics decrease calcium-activated potassium conductance in hippocampal pyramidal cells. Brain Res 407(1):159-162.
8. Lee K, McKenna F, Rowe IC, Ashford ML (1997) The effects of neuroleptic and tricyclic compounds on BKCa channel activity in rat isolated cortical neurones. Br J Pharmacol 121(8):1810-1816.
9. 2+ channels by the antipsychotic agent chlorpromazine. Acta Physiol Scand 173(4):401-408.
10. Zorumski CF, Yang J (1988) Non-competitive inhibition of GABA currents by phenothiazines in cultured chick spinal cord and rat hippocampal neurons. Neurosci Lett 92(1):86-91.
11. Schwartz RD, Mindlin MC (1988) Inhibition of the GABA receptor-gated chloride ion channel in brain by noncompetitive inhibitors of the nicotinic receptor-gated cation channel. J Pharmacol Exp Ther 244(3):963-970.
12. Mozrzymas JW, Barberis A, Michalak K, Cherubini E (1999) Chlorpromazine inhibits miniature GABAergic currents by reducing the binding and by increasing the unbinding rate of GABAA receptors. J Neurosci 19(7):2474-2488.
13. Sepúlveda MI, Baker J, Lummis SC (1994) Chlorpromazine and QX222 block 5-HT3 receptors in N1E-115 neuroblastoma cells. Neuropharmacology 33(3-4):493-499.
14. Lummis SC, Baker J (1997) Radioligand binding and photoaffinity labelling studies show a direct interaction of phenothiazines at 5-HT3 receptors. Neuropharmacology 36(4-5):665-670.
15. Xu Y, et al. (2006) Blocking of the nicotinic acetylcholine receptor ion channel by chlorpromazine, a noncompetitive inhibitor: A molecular dynamics simulation study. J Phys Chem B 110(41):20640-20648.
16. Arias HR (1998) Binding sites for exogenous and endogenous non-competitive inhibitors of the nicotinic acetylcholine receptor. Biochim Biophys Acta 1376(2):173-220.
17. Thompson AJ, Lester HA, Lummis S C R (2010) The structural basis of function in Cysloop receptors. Q Rev Biophys 43(4):449-499.
18. Miller PS, Smart TG (2010) Binding, activation and modulation of Cys-loop receptors. Trends Pharmacol Sci 31(4):161-174.
19. Brisson A, Unwin PN (1985) Quaternary structure of the acetylcholine receptor. Nature 315(6019):474-477.
20. Toyoshima C, Unwin N (1988) Ion channel of acetylcholine receptor reconstructed from images of postsynaptic membranes. Nature 336(6196):247-250.
21. Unwin N (1995) Acetylcholine receptor channel imaged in the open state. Nature 373(6509):37-43.
22. Miyazawa A, Fujiyoshi Y, Unwin N (2003) Structure and gating mechanism of the acetylcholine receptor pore. Nature 423(6943):949-955.
23. Brejc K, et al. (2001) Crystal structure of an ACh-binding protein reveals the ligandbinding domain of nicotinic receptors. Nature 411(6835):269-276.
24. Celie PHN, et al. (2004) Nicotine and carbamylcholine binding to nicotinic acetylcholine receptors as studied in AChBP crystal structures. Neuron 41(6):907-914.
25. Brams M, et al. (2011) A structural and mutagenic blueprint for molecular recognition of strychnine and d-tubocurarine by different cys-loop receptors. PLoS Biol 9(3):e1001034.
26. Tasneem A, Iyer LM, Jakobsson E, Aravind L (2005) Identification of the prokaryotic ligand-gated ion channels and their implications for the mechanisms and origins of animal Cys-loop ion channels. Genome Biol 6(1):R4.
27. Hilf RJC, Dutzler R (2008) X-ray structure of a prokaryotic pentameric ligand-gated ion channel. Nature 452(7185):375-379.
28. Hilf RJC, Dutzler R (2009) Structure of a potentially open state of a proton-activated pentameric ligand-gated ion channel. Nature 457(7225):115-118.
29. Bocquet N, et al. (2009) X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation. Nature 457(7225):111-114.
30. Hibbs RE, Gouaux E (2011) Principles of activation and permeation in an anionselective Cys-loop receptor. Nature 474(7349):54-60.
31. Althoff T, Hibbs RE, Banerjee S, Gouaux E (2014) X-ray structures of GluCl in apo states reveal a gating mechanism of Cys-loop receptors. Nature 512(7514):333-337.
32. Miller PS, Aricescu AR (2014) Crystal structure of a human GABAA receptor. Nature 512(7514):270-275.
33. Hassaine G, et al. (2014) X-ray structure of the mouse serotonin 5-HT3 receptor. Nature 512(7514):276-281.
34. Du J, Lü W, Wu S, Cheng Y, Gouaux E (2015) Glycine receptor mechanism elucidated by electron cryo-microscopy. Nature 526(7572):224-229.
35. Huang X, Chen H, Michelsen K, Schneider S, Shaffer PL (2015) Crystal structure of human glycine receptor-α3 bound to antagonist strychnine. Nature 526(7572):277-280.
36. Spurny R, et al. (2012) Pentameric ligand-gated ion channel ELIC is activated by GABA and modulated by benzodiazepines. Proc Natl Acad Sci USA 109(44):E3028-E3034.
37. Zimmermann I, Dutzler R (2011) Ligand activation of the prokaryotic pentameric ligand-gated ion channel ELIC. PLoS Biol 9(6):e1001101.
38. Pan J, et al. (2012) Structure of the pentameric ligand-gated ion channel ELIC cocrystallized with its competitive antagonist acetylcholine. Nat Commun 3:714.
39. Zimmermann I, Marabelli A, Bertozzi C, Sivilotti LG, Dutzler R (2012) Inhibition of the prokaryotic pentameric ligand-gated ion channel ELIC by divalent cations. PLoS Biol 10(11):e1001429.
40. Ulens C, et al. (2014) The prokaryote ligand-gated ion channel ELIC captured in a pore blocker-bound conformation by the Alzheimer's disease drug memantine. Structure 22(10):1399-1407.
41. Spurny R, et al. (2013) Multisite binding of a general anesthetic to the prokaryotic pentameric Erwinia chrysanthemi ligand-gated ion channel (ELIC). J Biol Chem 288(12):8355-8364.
42. Chen Q, et al. (2015) Direct pore binding as a mechanism for isoflurane inhibition of the pentameric ligand-gated ion channel ELIC. Sci Rep 5:13833.
43. Thompson AJ, Alqazzaz M, Ulens C, Lummis S C R (2012) The pharmacological profile of ELIC, a prokaryotic GABA-gated receptor. Neuropharmacology 63(4):761-767.
44. Oswald R, Changeux JP (1981) Ultraviolet light-induced labeling by noncompetitive blockers of the acetylcholine receptor from Torpedo marmorata. Proc Natl Acad Sci USA 78(6):3925-3929.
45. Changeux JP (1990) The TiPS lecture. The nicotinic acetylcholine receptor: An allosteric protein prototype of ligand-gated ion channels. Trends Pharmacol Sci 11(12):485-492.
46. Giraudat J, Dennis M, Heidmann T, Chang JY, Changeux JP (1986) Structure of the high-affinity binding site for noncompetitive blockers of the acetylcholine receptor: Serine-262 of the delta subunit is labeled by [3H]chlorpromazine. Proc Natl Acad Sci USA 83(8):2719-2723.
47. Revah F, et al. (1990) The noncompetitive blocker [3H]chlorpromazine labels three amino acids of the acetylcholine receptor gamma subunit: Implications for the alphahelical organization of regions MII and for the structure of the ion channel. Proc Natl Acad Sci USA 87(12):4675-4679.
48. Giraudat J, et al. (1987) Structure of the high-affinity binding site for noncompetitive blockers of the acetylcholine receptor: [3H]Chlorpromazine labels homologous residues in the beta and delta chains. Biochemistry 26(9):2410-2418.
49. Giraudat J, et al. (1989) The noncompetitive blocker [3H]chlorpromazine labels segment M2 but not segment M1 of the nicotinic acetylcholine receptor alpha-subunit. FEBS Lett 253(1-2):190-198.
50. Chiara DC, et al. (2009) [3H]Chlorpromazine photolabeling of the Torpedo nicotinic acetylcholine receptor identifies two state-dependent binding sites in the ion channel. Biochemistry 48(42):10066-10077.
51. Prevost MS, et al. (2012) A locally closed conformation of a bacterial pentameric proton-gated ion channel. Nat Struct Mol Biol 19(6):642-649.
52. Nemecz Á, Prevost MS, Menny A, Corringer P-J (2016) Emerging molecular mechanisms of signal transduction in pentameric ligand-gated ion channels. Neuron 90(3):452-470.
53. Plested A J R (2016) Structural mechanisms of activation and desensitization in neurotransmittergated ion channels. Nat Struct Mol Biol 23(6):494-502.
54. Spurny R, et al. (2015) Molecular blueprint of allosteric binding sites in a homologue of the agonist-binding domain of the α7 nicotinic acetylcholine receptor. Proc Natl Acad Sci USA 112(19):E2543-E2552.
55. Li S-X, et al. (2011) Ligand-binding domain of an α7-nicotinic receptor chimera and its complex with agonist. Nat Neurosci 14(10):1253-1259.
56. Huang S, et al. (2013) Complex between α-bungarotoxin and an α7 nicotinic receptor ligand-binding domain chimaera. Biochem J 454(2):303-310.
57. Pan J, et al. (2012) Structure of the pentameric ligand-gated ion channel GLIC bound with anesthetic ketamine. Structure 20(9):1463-1469.
58. Fourati Z, Sauguet L, Delarue M (2015) Genuine open form of the pentameric ligandgated ion channel GLIC. Acta Crystallogr D Biol Crystallogr 71(Pt 3):454-460.
59. Sauguet L, et al. (2013) Structural basis for ion permeation mechanism in pentameric ligand-gated ion channels. EMBO J 32(5):728-741.
60. Sauguet L, et al. (2014) Crystal structures of a pentameric ligand-gated ion channel provide a mechanism for activation. Proc Natl Acad Sci USA 111(3):966-971.
61. Sauguet L, Fourati Z, Prangé T, Delarue M, Colloc'h N (2016) Structural basis for xenon inhibition in a cationic pentameric ligand-gated ion channel. PLoS One 11(2):e0149795.
62. Nury H, et al. (2011) X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel. Nature 469(7330):428-431.
63. Sauguet L, et al. (2013) Structural basis for potentiation by alcohols and anaesthetics in a ligand-gated ion channel. Nat Commun 4:1697.
64. Hilf RJC, et al. (2010) Structural basis of open channel block in a prokaryotic pentameric ligand-gated ion channel. Nat Struct Mol Biol 17(11):1330-1336.
65. Galzi JL, Bertrand S, Corringer PJ, Changeux JP, Bertrand D (1996) Identification of calcium binding sites that regulate potentiation of a neuronal nicotinic acetylcholine receptor. EMBO J 15(21):5824-5832.
66. Changeux JP, Pinset C, Ribera AB (1986) Effects of chlorpromazine and phencyclidine on mouse C2 acetylcholine receptor kinetics. J Physiol 378:497-513.
67. Kabsch W (2010) XDS. Acta Crystallogr D Biol Crystallogr 66(Pt 2):125-132.
68. Winn MD, et al. (2011) Overview of the CCP4 suite and current developments. Acta Crystallogr D Biol Crystallogr 67(Pt 4):235-242.
69. Emsley P, Lohkamp B, Scott WG, Cowtan K (2010) Features and development of Coot. Acta Crystallogr D Biol Crystallogr 66(Pt 4):486-501.
70. Adams PD, et al. (2010) PHENIX: A comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66(Pt 2):213-221.
71. Chen VB, et al. (2010) MolProbity: All-atom structure validation for macromolecular crystallography. Acta Crystallogr D Biol Crystallogr 66(Pt 1):12-21.
72. Karlin A, Akabas MH (1998) Substituted-cysteine accessibility method. Methods Enzymol 293:123-145.
73. Eswar N, Eramian D, Webb B, Shen M-Y, Sali A (2008) Protein structure modeling with MODELLER. Methods Mol Biol 426:145-159.
74. Wolf MG, Hoefling M, Aponte-Santamaría C, Grubmüller H, Groenhof G (2010) g-membed: Efficient insertion of a membrane protein into an equilibrated lipid bilayer with minimal perturbation. J Comput Chem 31(11):2169-2174.
75. Abraham MJ, et al. (2015) GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1-2:19-25.
76. Lindorff-Larsen K, et al. (2010) Improved side-chain torsion potentials for the Amber ff99SB protein force field. Proteins 78(8):1950-1958.
77. Berger O, Edholm O, Jähnig F (1997) Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature. Biophys J 72(5):2002-2013.
78. Lundborg M, Lindahl E (2015) Automatic GROMACS topology generation and comparisons of force fields for solvation free energy calculations. J Phys Chem B 119(3):810-823.
79. Bussi G, Donadio D, Parrinello M (2007) Canonical sampling through velocity rescaling. J Chem Phys 126(1):014101.
80. Le Guilloux V, Schmidtke P, Tuffery P (2009) Fpocket: An open source platform for ligand pocket detection. BMC Bioinformatics 10:168.
81. Howard RJ, et al. (2011) Structural basis for alcohol modulation of a pentameric ligandgated ion channel. Proc Natl Acad Sci USA 108(29):12149-12154.
82. Humphrey W, Dalke A, Schulten K (1996) VMD: Visual molecular dynamics. J Mol Graph 14(1):33-38, 27-28.
83. Stone JE (1998) An efficient library for parallel ray tracing and animation. MS thesis (University of Missouri-Rolla, Rolla, MO).