Nicotinic acetylcholine receptor and the structural basis of neuromuscular transmission: Insights from Torpedo postsynaptic membranes

Quarterly Reviews of Biophysics

Volumn 46, Issue 4, 2014, Pages 283-322

  Unwin, Nigel ^a  

^a MRC LABORATORY OF MOLECULAR BIOLOGY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLCHOLINE; ION; LIPID; NICOTINIC RECEPTOR;

ANIMAL; BINDING SITE; CHEMICAL PHENOMENA; CHEMISTRY; CRYSTALLOGRAPHY; ELECTRON MICROSCOPY; FREEZE FRACTURE; METABOLISM; NEUROMUSCULAR SYNAPSE; PROTEIN BINDING; PROTEIN TERTIARY STRUCTURE; REVIEW; SYNAPTIC POTENTIAL; TORPEDO;

ACETYLCHOLINE; ALLOSTERIC SITE; ANIMALS; BINDING SITES; CRYSTALLOGRAPHY; FREEZE FRACTURING; HYDROPHOBIC AND HYDROPHILIC INTERACTIONS; IONS; LIPIDS; MICROSCOPY, ELECTRON; NEUROMUSCULAR JUNCTION; PROTEIN BINDING; PROTEIN STRUCTURE, TERTIARY; RECEPTORS, NICOTINIC; SYNAPTIC POTENTIALS; TORPEDO;

EID: 84887007845     PISSN: 00335835     EISSN: 14698994     Source Type: Journal    
DOI: 10.1017/S0033583513000061     Document Type: Review

References (149)

1. ADRIAN, A. M., DUBOCHET, J., LEPAULT, J. & MCDOWALL, A. W. (1984). Cryo-electron microscopy of viruses. Nature 308, 32-36.
2. ANDREEVA, I. E., NIRTHANAN, S., COHEN, J.B. & PEDERSEN, S. E. (2006). Site specificity of agonistinduced opening and desensitisation of the Torpedo californica nicotinic acetylcholine receptor. Biochemistry 45, 195-204.
3. AUERBACH, A. (2010). The gating isomerization of acetylcholine receptors. Journal of Physiology 588, 573-586.
4. AUERBACH, A. (2012). Thinking in cycles : MWC is a good model for acetylcholine receptor-channels. Journal of Physiology 590, 93-98.
5. BAKER, T. S., CASPAR, D. L. D. &MURAKAMI, W. T. (1983). Polyoma virus 'hexamer' tubes consist of paired pentamers. Nature 303, 446-448.
6. BECKSTEIN, O. & SANSOM, M. S. (2004). The influence of geometry, surface character and flexibility on the permeation of ions and water through biological pores. Physical Biology 1, 42-52.
7. BECKSTEIN, O. & SANSOM, M. S. (2006). A hydrophobic gate in an ion channel: the closed state of the nicotinic acetylcholine receptor. Physical Biology 3, 147-159.
8. BECKSTEIN, O., BIGGIN, P. C. & SANSOM, M. S. P. (2001). A hydrophobic gating mechanism for nanopores. Journal of Physical Chemistry B 105, 12902-12905.
9. BEROUKHIM, R. & UNWIN, N. (1997). Distortion correction of tubular crystals : improvements in the acetylcholine structure. Ultramicroscopy 70, 57-81.
10. BERRIMAN, J. & UNWIN, N. (1994). Analysis of transient structures by cryo-microscopy combined with rapid mixing of spray droplets. Ultramicroscopy 56, 241-252.
11. BIRKNER, J. P., POOLMAN, B. & KOçER, A. (2012). Hydrophobic gating of mechanosensitive channel of large conductance evidenced by single-subunit resolution. Proceedings of the National Academy of Sciences USA 10, 12944-12949.
12. BLANTON, M. P., DANGOTT, L. J., RAJA, S. K., LALA, A.K. & COHEN, J. B. (1998). Probing the structure of the nicotinic acetylcholine receptor ion channel with the uncharged photoactivable compound [3H]diazofluorene. Journal of Biological Chemistry 273, 8659-8668.
13. BOCQUET, N., NURY, H., BAADEN, M., LE POUPON, C., CHANGEUX, J.-P., DELARUE, M. & CORRINGER, P.-J. (2009). X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation. Nature 457, 375-379.
14. BRANNIGAN, G., HÉNIN, J., LAW, R., ECKENHOFF, R. & KLEIN, M. L. (2008). Embedded cholesterol in the nicotinic acetylcholine receptor. Proceedings of the National Academy of Sciences USA 105, 14418-14423.
15. BREJC, K., VAN DIJK, W. J., KLAASSEN, R. V., SCHURMANNS, M., VAN DER OOST, J., SMIT, A.B. & SIXMA, T.K. (2001). Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors. Nature 411, 260-276.
16. BRISSON, A. (1980). Etude structurale de proteines membranaires ay moyen des methodes optiques et numeriques d'analyse d'images de microscopie electronique. PhD thesis. University of Grenoble.
17. BRISSON, A. & UNWIN, P. N. T. (1984). Tubular crystals of acetylcholine receptor. Journal of Cell Biology 99, 1202-1211.
18. BRISSON, A. & UNWIN, P. N. T. (1985). Quaternary structure of the acetylcholine receptor. Nature 313, 474-477.
19. BUBLITZ, M., POULSEN, H., MORTH, J.P. & NISSEN, P. (2010). In and out of the cation pumps; P-type ATPase structure revisited. Current Opinion in Structural Biology 20, 431-439.
20. CARTAUD, J., BENEDETTI, E. L., SOBEL, A. & CHANGEUX, J.- P. (1978). A morphological study of the cholinergic receptor protein from Torpedo marmorata in its membrane environemnt and in its detergent-extracted purified form. Journal of Cell Science 29, 313-337.
21. CELIE, P. H. N., VAN ROSSUM-FIKKERT, S. E., VAN DIJK, W. J., BREJC, K., SMIT, A. B. & SIXMA, T.K. (2004). Nicotine and carbamylcholine binding to nicotinic acetylcholine receptors as studied in AChBP crystal structures. Neuron 41, 907-914.
22. CHAKRAPANI, S. & AUERBACH, A. (2005). A speed limit for conformational change of an allosteric membrane protein. Proceedings of the National Academy of Sciences USA 102, 87-92.
23. CHANG, H.W. & BOCK, E. (1977). Molecular forms of acetylcholine receptor. Effects of calcium ions ans a sulfhydryl reagent on the occurrence of oligomers. Biochemistry 16, 4513-4520.
24. CHANG, G., SPENCER, R. H., LEE, A. T., BARCLAY, M. T. & REES, D. C. (1998). Structure of the MscL homolog from Mycobacterium tuberculosis : a gated mechanosensitive ion channel. Science 282, 2220-2226.
25. CHANGEUX, J.-P. & EDELSTEIN, S. J. (2005). Allosteric mechanisms of signal transduction. Science 308, 1424-1428.
26. COLQUHOUN, D. & SAKMANN, B. (1985). Fast events in single-channel currents activated by acetylcholine and its analogues at the frog muscle end-plate. Journal of Physiology 369, 501-557.
27. COLQUHOUN, D. &OGDEN, D. C. (1988). Activation of ion channels in the frog endplate by high concentrations of acetylcholine. Journal of Physiology 395, 131-159.
28. COLQUHOUN, D., SHELLEY, C., HATTON, C., UNWIN, N. & SIVILOTTI, L. (2003). Nicotinic Acetylcholine Receptors. In Burger's Medicinal Chemistry Drug Discovery, 6th edn, vol. 2 (ED. D. J. Abraham), New York: John Wiley, pp. 357-405.
29. COUDRAY, N., VALVO, S., HU, M., LASALA, R., KIM, C., VINK, M., ZHOU, M., PROVASI, D., FILIZOLA, M., TAO, J., FANG, J., PENCZENK, P. A., UBARRETXENA-BELANDIA, I. & STOKES, D. L. (2013). Inward-facing conformation of the zinc transporter YiiP revealed by cryoelectron microscopy. Proceedings of the National Academy of Sciences USA 110, 2140-2145.
30. CORRINGER, P.-J., POITEVIN, F., PREVOST, M. S., SAUGUET, L., DELARUE, M., CHANGEUX, J.-P. (2012). Structure and pharmacology of pentameric receptor channels: from bacteria to brain. Structure 20, 941-956.
31. CORRY, B. (2006). An energy-efficient gating mechanism in the acetylcholine receptor channel suggested by molecular and Brownian dynamics. Biophysical Journal 90, 799-810.
32. CYMES, G.D. & GROSMAN, C. (2008). Pore-opening mechanism of the nicotinic acetylcholine receptor evinced by proton transfer. Nature Structure and Molecular Biology 15, 389-396.
33. CYMES, G. D., NI, Y. & GROSMAN, C. (2005). Probing ion channel pores one proton at a time. Nature 438, 975-980.
34. DACOSTA, C. J. B.,MEDAGLIA, S. A., LAVIGNE, N.,WANG, S., CARSWELL, C.L. & BAENZIGER, J. E. (2009). Anionic lipids allosterically modulate multiple nicotinic acetylcholine receptor conformational equilibria. Journal of Biological Chemistry 284, 33841-33849.
35. DACOSTA, C. J. B., FREE, C. R., CORRADI, J., BOUZAT, C. & SINE, S. M. (2011). Single-channel and structural foundations of neuronal a7 acetylcholine receptor potentiation. Journal of Neuroscience 31, 13870-13879.
36. DALE, H.H. & DUDLEY, H. W. (1929). The presence of histamine and acetylcholine in the spleen of the ox and horse. Journal of Physiology 68, 97-123.
37. DALZIEL, A. W., ROLLINS, E. S. &MCNAMEE, M. G. (1980). The effect of cholesterol on agonist-induced flux in reconstituted acetylcholine receptor vesicles. FEBS Letters 122, 193-196.
38. DELLISANTI, C. D., YAO, Y., STROUD, J. C., WANG, Z-Z. & CHEN, L. (2007). Crystal structure of the extracellular domain of nAChR a1 bound to a-bungarotoxin at 1.94 A ? resolution. Nature Neuroscience 10, 953-962.
39. DEROSIER, D. J. (2000). Correction of high resolution data for curvature of the Ewald sphere. Ultramicroscopy 81, 83-98.
40. DEROSIER, D. J. & KLUG, A. (1968). Reconstruction of three-dimensional structures from electron micrographs. Nature 217, 130-134.
41. DEROSIER, D. J. & MOORE, P. B. (1970). Reconstruction of three-dimensional images from electron micrographs of structures with helical symmetry. Journal of Molecular Biology 52, 355-369.
42. DIPAOLA, M., CZAJKOWSKI, C. & KARLIN, A. (1989). The sidedness of the COOH terminus of the acetylcholine receptor delta subunit. Journal of Biological Chemistry 264, 15457-15463.
43. DILGER, J. P. & BRETT, R. S. (1990). Direct measurement of the concentration- and time-dependent open probability of the nicotinic acetylcholine receptor channel. Biophysical Journal 57, 723-731.
44. DOYLE, D. A., MORAIS CABRAL, J., PFUETZNER, R. A., KUO, A., GULBIS, J. M., COHEN, S. L., CHAIT, B.T. & MACKINNON, R. (1998). The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280, 69-77.
45. DUBOCHET, J., ADRIAN, M., CHANG, J.-J., HOMO, J. C., LEPAULT, J., MCDOWALL, A.W. & SCHULZ, P. (1988). Cryo-electron microscopy of vitrified specimens. Quarterly Reviews of Biophysics 21, 129-228.
46. EGELMAN, E. H. (2007). The iterative helical real space reconstruction method: surmounting the problems posed by polymers. Journal of Structural Biology 157, 83-94.
47. EISELÉ, J.-L., BERTRAND, S., GALZI, J.-L., DEVILLERSTHIÉRY, A., CHANGEUX, J.-P. & BERTRAND, D. (1993). Chimaeric nicotinic-serotonergic receptor combines distinct ligand binding and channel specificities. Nature 366, 479-483.
48. ENGEL, A. G., OHNO, K. & SINE, S. M. (2003). Sleuthing molecular targets for neurological diseases: the neuromuscular junction as a paradigm. Nature Reviews Neuroscience 4, 339-352.
49. FILATOV, G.N. & WHITE, M. M. (1995). The role of conserved leucines in the M2 domain of the acetylcholine receptor in gating. Molecular Pharmacology 48, 379-384.
50. FISHER, L. S., WARD, A., MILLIGAN, R. A., UNWIN, N., POTTER, C. S. & CARRAGHER, B. (2011). A helical processing pipeline for EM structure determination of membrane proteins. Methods 55, 350-362.
51. FUJIYOSHI, Y. (1998). The structural study of membrane proteins by electron crystallography. Advances in Biophysics 35, 27-74.
52. FUJIYOSHI, Y., MIZUASAKI, T., MORIKAWA, K., YAMAGISHI, H., AOKI, Y., KIHARA, H. & HARADA, Y. (1991). Development of a superfluid helium stage for high resolution electron microscopy. Ultramicroscopy 38, 241-251.
53. GAO, F., BREN, N., BURGHARDT, T. P., HANSEN, S., HENCHMAN, R. H., TAYLOR, P., MCCAMMON, J.A. & SINE, S. M. (2005). Agonist-mediated conformational changes in acetylcholine-binding protein revealed by simulation and intrinsic tryptophan fluorescence. Journal of Biochemistry 280, 8443-8451.
54. GIERSIG, M., KUNATH, W., PRIBILLA, I., BANDINI, G. & HUCHO, F. (1989). Symmetry and dimensions of membrane- bound nicotinic acetylcholine receptors from Torpedo californica tissue : rapid rearrangement to two-dimensional ordered lattices. Membrane Biochemistry 8, 81-93.
55. GILL, J. K., SAVOLAINEN, M., YOUNG, G. T., ZWART, R., SHER, E. & MILLAR, N. S. (2011). Agonist activation of a7 nicotinic acetylcholine receptors via an allosteric membrane site. Proceedings of the National Academy of Sciences USA 108, 5867-5872.
56. GIRAUDAT, J., DENNIS, M., HEIDMANN, T., CHANG, J.-Y. & CHANGEUX, J. P. (1986). Structure of the the high-affinity binding site for noncompetitive blockers of the acetylcholine receptor:serine-262 of the d subunit is labelled by [3H]chlorpromazine. Proceedings of the National Academy of Sciences USA 83, 2719-2723.
57. GONZALEZ-GUTIERREZ G. & GROSMAN, C. (2010). Bridging the gap between structural models of nicotinic receptor superfamily ion channels and their corresponding functional states. Journal of Molecular Biology 403, 693-705.
58. GONZALEZ-GUTIERREZ, G., LUKK, T., AGARWAL, V., PAPKE, D., NAIR, S.K. & GROSMAN, C. (2012). Mutations that stabilise the open state of the Erwinia chrisanthemi ligandgated ion channel fail to change the conformation of the pore domain in crystals. Proceedings of the National Academy of Sciences USA 109, 6331-6336.
59. GOUAUX, E. (2004). Structure and function of AMPA receptors. Journal of Physiology 554, 249-253.
60. GRUTTER, T. & CHANGEUX, J.-P. (2001). Nicotinic receptors in wonderland. Trends in Biochemical Sciences 26, 459-463.
61. GRUTTER, T., DE CARVALHO, L. P., DUFRESNE, V., TALY, A., EDELSTEIN, S. J. & CHANGEUX, J.-P. (2005). Molecular tuning of fast gating in pentameric ligand-gated ion channels. Proceedings of the National Academy of Sciences USA 102, 18207-18212.
62. HALES, T. G., DUNLOP, J. I., DEEB, T. Z., CARLAND, J. E., KELLEY, S. P., LAMBERT, J. J. & PETERS, J. A. (2006). Common determinants of single channel conductance within the large cytoplasmic loop of 5-hydroxytryptamine type 3 and a4b2 nicotinic acetylcholine receptors. Journal of Biological Chemistry 281, 8062-8071.
63. HANEK, A. P., LESTER, H. A. & DOUGHERTY, D. A. (2008). A stereochemical test of a proposed structural feature of the nicotinic acetylcholine receptor. Journal of the American Chemical Society 130, 13216-13218.
64. HENDERSON, R. & UNWIN, P. N. T. (1975). Threedimensional model of the purple membrane obtained by electron microscopy. Nature 257, 28-32.
65. HENDERSON, R., BALDWIN, J. M., DOWNING, K. H., LEPAULT, J. & ZEMLIN, F. (1986). Structure of purple membrane from halobacterium halobium: recording, measurement and evaluation of electron micrographs at 3.5 A ? resolution. Ultramicroscopy 19, 147-178.
66. HEUSER, J.E. & SALPETER, M. (1979). Organization of acetylcholine receptors in quick-frozen, deep-etched, and rotary-replicated Torpedo postsynaptic membrane. Journal of Cell Biology 82, 150-173.
67. HIBBS, R. E. & GOUAUX, E. (2011). Principles of activation and permeation in an anion-selective Cys-loop receptor. Nature 474, 54-60.
68. HILF, R. J. & DUTZLER, R. (2008). X-ray structure of a prokaryotic pentameric ligand-gated ion channel. Nature 452, 375-379.
69. HILF, R. J.&DUTZLER, R. (2009). Structure of a potentially open state of a proton-activated pentameric ligandgated ion channel. Nature 457, 115-118.
70. HOSIE, A. M., WILKINS, M. E., DA SILVA, H.M. & SMART, T. G. (2006). Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites. Nature 444, 486-489.
71. HUCHO, F., OBERTHUR, W. & LOTTSPEICH, F. (1986). The ion channel of the nicotinic acetylcholine receptor is formed by the homologous helices MII of the receptor subunits. FEBS Letters 205, 137-142.
72. IMOTO, K., METHFESSEL, C., SAKMANN, B., MISHINA, M., MORI, Y., KONNO, T., FUKUDA, K., KURASAKI, M., BUJO, H., FUJITA, Y. & NUMA, S. (1986). Location of a d-subunit region determining ion transport through the acetylcholine receptor channel. Nature 324, 670-674.
73. IMOTO, K., BUSCH, C., SAKMANN, B., MISHINA, M., KONNO, T., NAKAI, J., BUJO, H., FUKUDA, K.&NUMA, S. (1988). Rings of negatively charged amino acids determine the acetylcholine receptor channel conductance. Nature 335, 645-648.
74. IMOTO, K., KONNO, T., NAKAI, J.,WANG, F., MISHINA, M.& NUMA, S. (1991). A ring of uncharged polar amino acids as a component of channel constriction in the nicotinic acetylcholine receptor. FEBS Letters 289, 193-200.
75. JACKSON, M. B. (1986). Kinetics of unliganded acetylcholine receptor channel gating. Biophysical Journal 49, 663-672.
76. JACKSON, M. B. (1988). Dependence of acetylcholine receptor channel kinetics on agonist concentration in cultured mouse muscle fibres. Journal of Physiology 397, 555-583.
77. JACKSON, M. B. (1989). Perfection of a synaptic receptor: kinetics and energetics of the acetylcholine receptor. Proceedings of the National Academy of Sciences USA 86, 2199-2203.
78. JHA, A., CADUGAN, D. J., PUROHIT, P. & AUERBACH, A. (2007). Acetylcholine receptor gating at extracellular domain interface : the Cys-loop and M2-M3 linker. Journal of General Physiology 130, 547-558.
79. KARLIN, A. (1993). Structure of nicotinic acetylcholine receptors. Current Opinions in Neurobiology 3, 299-309.
80. KARLIN, A. (2002). Emerging structure of the nicotinic acetylcholine receptors. Nature Reviews Neuroscience 3, 102-114.
81. KARLSSON, E., HEILBRONN, E. & WIDLUND, L. (1972). Isolation of the nicotinic acetylcholine receptor by bispecific chromatography on insolubilized Naja Naja neurotoxin. FEBS Letters 28, 107-111.
82. KELLEY, S. P., DUNLOP, J. I., KIRKNESS, E. F., LAMBERT, J. J. & PETERS, J. A. (2003). A cytoplasmic region determines single-channel conductance in 5-HT3 receptors. Nature 424, 321-324.
83. KISTLER, J. & STROUD, R. M. (1981). Crystalline arrays of membrane-bound acetylcholine receptor. Proceedings of the National Academy of Sciences USA 78, 3678-3682.
84. KRAUSE, R. M., BUISSON, B., BERTRAND, S., CORRINGER, P.-J., GALZI, J. L., CHANGEUX, J.-P. & BERTRAND, D. (1998). Ivermectin: a positive allosteric effector of the alpha7 neuronal nicotinic acetylcholine receptor. Molecular Pharmacology 53, 283-294.
85. KUBALEK, E., RALSTON, S., LINDSTROM, J. & UNWIN, N. (1987). Location of subunits within the acetylcholine receptor be elctron image analysis of tubular crystals from Torpedo marmorata. Journal of Cell Biology 105, 9-18.
86. KUHLBRANDT, W., WANG, D.N. & FUJIYOSHI, Y. (1994). Atomic model of plant light-harvesting complex by electron crystallography. Nature 367, 614-621.
87. KUFFLER, S.W. & YOSHIKAMI, D. (1975). The number of transmitter molecules in a quantum: an estimate from iontophoretic application of acetylcholine at the neuromuscular junction. Journal of Physiology 251, 465-482.
88. LABARCA, C., NOWAK, M. W., ZHANG, H., TANG, L., DESHPANDE, P. & LESTER, H. A. (1995). Channel gating governed symmetrically by conserved leucine residues in the M2 domain of nicotinic receptors. Nature 376, 514-516.
89. LAPE, R., COLQUHOUN, D. & SIVILOTTI, L. G. (2008). On the nature of partial agonism in the nicotinic receptor superfamily. Nature 454, 722-727.
90. LEE, W.Y. & SINE, S. M. (2005). Principal pathway coupling agonist binding to channel gating in nicotinic receptors. Nature 438, 243-247.
91. LEE, W. Y., FREE, C. R. & SINE, S. M. (2009). Binding to gating transduction in nicotinic receptors: Cys-loop energetically couples to pre-M1 and M2-M3 regions. Journal of Neuroscience 29, 3189-3199.
92. LEONARD, R. J., LABARCA, C. G., CHARNET, P., DAVIDSON, N. & LESTER, H. A. (1988). Evidence that the M2 membrane-spanning region lines the ion channel pore of the nicotinic receptor. Science 242, 1578-1581.
93. LESTER, H. A., DIBAS, M. I., DAHAN, D. S., LEITE, J. F. & DOUGHERTY, D. A. (2004). Cys-loop receptors: new twists and turns. Trends in Neurosciences 27, 329-336.
94. LI, G.-D., CHIARA, D. C., SAWYER, G. W., HUSAIN, S. S., OLSEN, R.W. & COHEN, J. B. (2006). Identification of a GABAA receptor anesthetic binding site at subunit interfaces by photolabeling with an etomidate analog. Journal of Neuroscience 26, 11599-11605.
95. LOCHER, K. P. (2009). Structure and mechanism of ATP-binding cassette transporters. Philosophical Transactions of the Royal Society London B Biological Sciences 364, 239-245.
96. LU, Z., SHAIKH, T. R., BARNARD, D., MENG, X., MOHAMED, H., YASSIN, A., MANNELLA, C. C., AGRAWAL, R. K., LU, T.M. & WAGENKNECHT, T. (2009). Monolithic microfluidic mixing-spraying devices for time-resolved cryo-electron microscopy. Journal of Structural Biology 168, 388-395.
97. MACONOCHIE, D. J., FLETCHER, G.H. & STEINBACH, J.H. (1995). The conductance of the muscle nicotinic receptor channel changes rapidly on gating. Biophysical Journal 68, 483-490.
98. MASCIA, M. P., TRUDELL, J.R. & HARRIS, R. A. (2000). Specific binding sites for alcohols and anesthetics on ligand-gated ion channels. Proceedings of the National Academy of Sciences USA 97, 9305-9310.
99. MÉNÉTRET, J. F., HOFMANN, W., SCHRÖDER, R. R., RAPP, G. & GOODY, R. S. (1991). Time-resolved cryo-electron microscopic study of the dissociation of actomyosin induced by photolysis of photolabile nucleotides. Journal of Molecular Biology 219, 139-144.
100. MILEDI, R., MOLINOFF, P. & POTTER, L. T. (1971). Isolation of the cholinergic receptor protein of Torpedo electric tissue. Nature 229, 554-557.
101. MILLAR, N. S. & GOTTI, C. (2009). Diversity of vertebrate nicotinic acetylcholine receptors. Neuropharmacology 56, 237-246.
102. MITRA, A., CYMES, G.D. & AUERBACH, A. (2005). Dynamics of the acetylcholine receptor pore at the gating transition state. Proceedings of the National Academy of Sciences USA 102, 15069-15074.
103. MITRA, A. K., MCCARTHY, M. P. & STROUD, R. M. (1989). Three-dimensional structure of the nicotinic acetylcholine receptor and location of the major associated 43-kD cytoskeletal protein, determined at 22 A ? by low dose electron microscopy and x-ray diffraction to 12.5 A ? . Journal of Cell Biology 109, 755-774.
104. MIYAZAWA, A., FUJIYOSHI, Y., STOWELL, M. & UNWIN, N. (1999). Nicotinic acetylcholine receptor at 4.6 A ? resolution: transverse tunnels in the channel wall. Journal of Molecular Biology 288, 765-786.
105. MIYAZAWA, A., FUJIYOSHI, Y. & UNWIN, N. (2003). Structure and gating mechanism of the acetylcholine receptor pore. Nature 423, 949-955.
106. MONOD, J., WYMAN, J. & CHANGEUX, J.-P. (1965). On the nature of allosteric transitions: a plausible model. Journal of Molecular Biology 12, 88-118.
107. MORICONI, C., DI CASTRO, M. A., FUCILE, S., EUSEBI, F. & GRASSI, F. (2010). Mechanism of verapamil action on wild-type and slow-channel mutant human muscle acetylcholine receptor. Journal of Neurochemistry 114, 1231-1240.
108. MUKHTASIMOVA, N., LEE,W. Y.,WANG, H. L. & SINE, S.M. (2009). Detection and trapping of intermediate states priming nicotinic receptor channel opening. Nature 459, 451-454.
109. NEHER, E. & SAKMANN, B. (1976). Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature 260, 799-802.
110. NELSON, N., ANHOLT, R., LINDSTROM, J. & MONTAL, M. (1980). Reconstitution of purified acetylcholine receptors with functional ion channels in planar lipid bilayers. Proceedings of the National Academy of Sciences USA 77, 3057-3061.
111. NODA, M., TAKAHASHI, H., TANABE, T., TOYOSATO, M., KIKYOTANI, S., FURUTANI, Y., HIROSE, T., TAKASHIMA, H., INAYAMA, S., MIYATA, T. & NUMA, S. (1983). Structural homology of Torpedo californica acetylcholine receptor subunits. Nature 302, 528-532.
112. OLSEN, R. W., MEUNIER, J. C. & CHANGEUX, J.-P. (1972). Progress in the purification of the cholinergic receptor protein from Electrophorus electricus by affinity chromatography. FEBS Letters 28, 96-100.
113. PAAS, Y., GIBOR, G., GRAILHE, R., SAVATIER-DUCLERT, N., DUFRESNE, V., SUNESEN, M., DE CARVALHO, L. P., CHANGEUX, J.-P. & ATTALI, B. (2005). Pore conformations and gating mechanism of a Cys-loop receptor. Proceedings of the National Academy of Sciences USA 102, 15877-15882.
114. PERUTZ, M. F. (1989). Mechanisms of cooperativity and allosteric regulation in proteins. Quarterly Reviews of Biophysics 22, 139-236.
115. POMFRET, A. J., RICE, W.J. & STOKES, D. L. (2007). Application of the iterative helical real-space reconstruction method to large membranous tubular crystals of P-type ATPases. Journal of Structural Biology 157, 106-116.
116. PREVOST, M. S., SAUGUET, L., NURY, H., VAN RENTERGHEM, C., HUON, C., POLTEVIN, F., BAADEN, M., DELARUE, M.&CORRINGER, P.-J. (2012). A locally closed conformation of a bacterial pentameric proton-gated ion channel. Nature Structure and Molecular Biology 19, 642-649.
117. ROSS, M. J., KLYMKOWSKI, M. W., AGARD, D.A. & STROUD, R. M. (1977). Structural studies of a membranebound acetylcholine receptor from Torpedo californica. Journal of Molecular Biology 116, 635-659.
118. SAKMANN, B., METHFESSEL, C., MISHINA, M., TAKAHASHI, T., TAKAI, T., KURASAKI, K., FUKUDA, K.&NUMA, S. (1985). Role of acetylcholine receptor subunits in gating of the channel. Nature 18, 538-543.
119. SEALOCK, R., WRAY, B.E. & FROEHNER, S. C. (1984). Ultrastructural localisation of the Mr 43,000 protein and the acetylcholine receptor in Torpedo postsynaptic membranes using monoclonal antibodies. Journal of Cell Biology 98, 2239-2244.
120. SINE, S. M. (2002). The nicotinic receptor ligand binding domain. Journal of Neurobiology 53, 431-446.
121. SINE, S. M. (2012). End-plate acetylcholine receptor: structure, mechanism, pharmacology and disease. Physiological Reviews 92, 1189-1234.
122. SINE, S.M. & ENGEL, A. G. (2006). Recent advances in Cys-loop receptor structure and function. Nature 440, 448-455.
123. SINE, S. M., CLAUDIO, T. & SIGWORTH, F. J. (1990). Activation of Torpedo acetylcholine receptors expressed in mouse fibroblasts. Single channel current kinetics reveal distinct agonist binding affinities. Journal of General Physiology 96, 395-437.
124. SINE, S. M., KREIENKAMP, H.-J., BREN, N., MAEDA, R. & TAYLOR, P. (1995). Molecular dissection of subunit interfaces in the acetylcholine receptor; identification of determinantsof a-conotoxin M1 selectivity. Neuron 15, 205-211.
125. SONG, C. & CORRY, B. (2009). Role of acetylcholine receptor domains in ion selectivity. Biochimica et Biophysica Acta 1788, 1466-1473.
126. TANI, K., MITSUMA, T., HIROAKI, Y., KAMEGAWA, A., NISHIKAWA, K., TANIMURA, Y. & FUJIYOSHI, Y. (2009). Mechanism of aquaporin-4's fast and highly selective water conduction and proton exclusion. Journal of Molecular Biology 389, 694-706.
127. TASNEEM, A., LYER, L. M., 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 Biology 6, R4.
128. THOMPSON, A. J., LESTER, H. A. & LUMMIS, S. C. R. (2010). The structural basis of function in Cys-loop receptors. Quarterly Reviews of Biophysics 43, 449-499.
129. TOYOSHIMA, C. & UNWIN, N. (1990). Three-dimensional structure of the acetylcholine receptor by cryoelectron microscopy and helical image reconstruction. Journal of Cell Biology 111, 2623-2635.
130. TOYOSHIMA, C. & UNWIN, N. (1988). Ion channel of acetylcholine receptor reconstructed from images of postsynaptic membranes. Nature 336, 247-250.
131. TZARTOS, S. J. & LINDSTROM, J. M. (1980). Monoclonal antibodies used to probe acetylcholine receptor structure: Localization of the main immunogenic region and detection of similarities between subunits. Proceedings of the National Academy of Sciences USA 77, 755-759.
132. UNWIN, N. (1993). Nicotinic acetylcholine receptor at 9 A ? resolution. Journal of Molecular Biology 229, 1101-1124.
133. UNWIN, N. (1995). Acetylcholine receptor channel imaged in the open state. Nature 373, 37-43.
134. UNWIN, N. (1996). Projection structure of the nicotinic acetylcholine receptor: distinct conformations of the a subunits. Journal of Molecular Biology 257, 586-596.
135. UNWIN, N. (2000) The Croonian lecture 2000. Nicotinic acetylcholine receptor and the structural basis of fast synaptic transmission. Philosophical Transactions of the Royal Society London B 355, 1813-1829.
136. UNWIN, N. (2005). Refined structure of the nicotinic acetylcholine receptor at 4 A ? resolution. Journal of Molecular Biology 346, 967-989.
137. UNWIN, N. & FUJIYOSHI, Y. (2012). Gating movement of acetylcholine receptor caught by plunge-freezing. Journal of Molecular Biology 422, 617-634.
138. UNWIN, P.N.T. & HENDERSON, R. (1975). Molecular structure determination by electron microscopy of unstained crystalline specimens. Journal of Molecular Biology 94, 425-440.
139. VILLARROEL, A., HERLITZE, S., KOENEN, M. & SAKMANN, B. (1991). Location of a threonine residue in the a-subunit M2 transmembrane segment that determines the ion flow through the acetylcholine receptor channel. Proceedings of the Royal Society London B243, 69-74.
140. WANG, H.-L., CHENG, X., TAYLOR, P., MCCAMMON, J. A. & SINE, S. M. (2008). Control of cation permeation through the nicotinic receptor channel. PLoS Computational Biology 4, e41.
141. WANG, H.-L., TOGHRAEE, R., PAPKE, D., CHENG, X.-L., MCCAMMON, J. A., RAVAIOLI, U. & SINE, S. M. (2009). Single-channel current through nicotinic receptor produced by closure of binding site loop. Biophysical Journal 96, 3582-3590.
142. WHITE, B.H. & COHEN, J. B. (1992). Agonist-induced changes in the structure of the acetylcholine receptor M2 regions revealed by photoincorporation of an uncharged nicotinic noncompetitive antagonist. Journal of Biological Chemistry 267, 15770-15783.
143. WHITE, H. D., THIRUMURUGAN, K., WALKER, M.L. & TRINICK, J. (2003). A second generation apparatus for time-resolved electron cryomicroscopy using stepper motors and electrospray. Journal of Structural Biology 144, 246-252.
144. WILSON, G.G. & KARLIN, A. (1998). The location of the gate in the acetylcholine receptor channel. Neuron 20, 1269-1281.
145. XIE, Y. & COHEN, J. B. (2001). Contributions of Torpedo nicotinic acetylcholine receptor cTrp-55 and d-Trp-57 to agonist and competitive antagonist function. Journal of Biological Chemistry 276, 2417-2426.
146. XIU, X., HANEK, A. P., WANG, J., LESTER, H.A. & DOUGHERTY, D. A. (2005). A unified view of the role of electrostatic interactions in modulating the gating of Cys loop receptors. Journal of Biological Chemistry 280, 41655-41666.
147. YOUNG, G. T., ZWART, R., WALKER, A. S., SHER, E. & MILLAR, N. S. (2008). Potentiation of alpha7 nicotinic acetylcholine receptors via an allosteric transmembrane site. Proceedings of the National Academy of Sciences USA 105, 14686-14691.
148. ZHONG, W., GALLIVAN, J. P., ZHANG, Y., LI, L., LESTER, H. A. & DOUGHERTY, D. A. (1998). From ab initio quantum mechanics to molecular neurobiology: a cation- pi binding site in the nicotinic receptor. Proceedings of the National Academy of Sciences USA 95, 12008-12093.
149. ZIMMERMANN, I. & DUTZLER, R. (2011). Ligand activation of the prokaryotic pentameric ligand-gated ion channel ELIC. PLoS Biology 9, e1001101.