The pore domain of the nicotinic acetylcholine receptor: Molecular modeling, pore dimensions, and electrostatics

Biophysical Journal

Volumn 71, Issue 4, 1996, Pages 1659-1671

  Sankararamakrishnan, R ^a,b   Adcock, C ^a   Sansom, Mark S P ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ION CHANNEL; NICOTINIC RECEPTOR;

ARTICLE; COMPUTER MODEL; ELECTRICITY; MOLECULAR DYNAMICS; TORPEDO;

EID: 0029813087     PISSN: 00063495     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0006-3495(96)79370-0     Document Type: Article

References (79)

1. Akabas, M. H., C. Kauffmann, P. Archdeacon, and A. Karlin. 1994. Identification of acetylcholine receptor channel-lining residues in the entire M2 segment of the α subunit. Neuron. 13:919-927.
2. Akabas, M. H., D. A. Stauffer, M. Xu, and A. Karlin. 1992. Acetylcholine receptor channel structure probed in cysteine-substitution mutants. Science. 258:307-310.
3. Bechinger, B., Y. Kim, L. E. Chirlian, J. Gesell, J. M. Neumann, M. Montai, J. Tomich, M. Zasloff, and S. J. Opella. 1991. Orientations of amphipathic helical peptides in membrane bilayers determined by solid-state NMR spectroscopy. J. Biomol. NMR. 1:167-173.
4. Bertrand, D., J. L. Galzi, A. Devillers-Thiéry, S. Bertrand, and J. P. Changeux. 1993. Stratification of the channel domain in neurotransmitter receptors. Curr. Opin. Cell Biol. 5:688-693.
5. Breed, J., I. D. Kerr, R. Sankararamakrishnan, and M. S. P. Sansom. 1995. Packing interactions of Aib-containing helices: molecular modelling of parallel dimers of simple hydrophobic helices and of alamethicin. Blopolymers. 35:639-655.
6. Breed, J., R. Sankararamakrishnan, I. D. Kerr, and M. S. P. Sansom. 1996. Molecular dynamics simulations of water within models of transbilayer pores. Biophys. J. 70:1643-1661.
7. Brooks, B. R., R. E. Bruccoleri, B. D. Olafson, D. J. States, S. Swaminathan, and M. Karplus. 1983. CHARMM: a program for macromolecular energy, minimisation, and dynamics calculations. J. Comp. Chem. 4:187-217.
8. Brünger, A. T. 1992. X-PLOR Version 3.1. A System for X-ray Crystallography and NMR. Yale University Press, New Haven, CT.
9. Changeux, J. P., J. I. Galzi, A. Devillers-Thiéry, and D. Bertrand. 1992. The functional architecture of the acetylcholine nicotinic receptor explored by affinity labelling and site-directed mutagenesis. Q. Rev. Biophys. 25:395-432.
10. Charnet, P., C. Labarca, R. J. Leonard, N. J. Vogelaar, L. Czyzyk, A. Gouin, N. Davidson, and H. A. Lester. 1990. An open-channel blocker interacts with adjacent turns of α-helices in the nicotinic acetylcholine receptor. Neuron. 2:87-95 .
11. Chiu, S. W., E. Jakobsson, S. Subramanian, and J. A. McCammon. 1991. Time-correlation analysis of simulated water motion in flexible and rigid gramicidin channels. Biophys. J. 60:273-285.
12. + permeability ratios of nicotinic acetylcholine receptors are reduced by mutations near the intracellular end of the M2 region. J. Gen. Physiol. 99:545-572.
13. Couturier, S., D. Bertrand, J.-M. Matter, M.-C. Hernandez, S. Bertrand, N. Millar, S. Valera, T. Barkas, and M. Ballivet. 1990. A neuronal nicotinic acetylcholine receptor subunit (alpha 7) is developmentally regulated and forms a homooligomeric channel blocked by alpha BTX. Neuron. 5:847-856.
14. Davis, M. E., J. D. Madura, B. A. Luty, and J. A. McCammon. 1991. Electrostatics and diffusion of molecules in solution: simulations with the University of Houston Brownian dynamics program. Comput. Phys. Comm. 62:187-197.
15. Dorman, V., M. B. Partenskii, and P. C. Jordan. 1996. A semi-microscopic Monte Carlo study of permeation energetics in a gramicidin-like channel: the origin of cation selectivity. Biophys. J. 70:121-134.
16. Dwyer, T. M., D. J. Adams, and B. Hille. 1980. The permeability of the endplate channel to organic cations in frog muscle. J. Gen. Physiol. 75:469-492.
17. Eisenman, G., and O. Alvarez. 1991. Structure and function of channels and channelogs as studied by computational chemistry. J. Membr. Biol. 119:109-132.
18. Eisenman, G., and J. A. Dani. 1987. An introduction to molecular architecture and permeability of ion channels. Annu. Rev. Biophys. Biophys. Chem. 16:205-226.
19. Engels, M., D. Bashford, and M. R. Ghadiri. 1995. Structure and dynamics of self-assembling peptide nanotubes and the channel-mediated water organization and self-diffusion. A molecular dynamics study. J. Am. Chem. Soc. 117:9151-9158.
20. Filatov, G. N., and M. M. White. 1995. The role of conserved leucines in the M2 domain of the acetylcholine-receptor in channel gating. Mol. Pharmacol. 48:379-384.
21. Furois-Corbin, S., and A. Pullman. 1989a. Energy profiles in the acetyl-choline receptor (AChR) channel. FEBS Lett. 252:63-68.
22. Furois-Corbin, S., and A. Pullman. 1989b. A possible model for the inner wall of the acetylcholine receptor channel. Biochim. Biophys. Acta. 984:339-350.
23. Furois-Corbin, S., and A. Pullman. 1991. The effect of point mutations on energy profiles in a model of the nicotinic acetylcholine (AChR) channel. Biophys. Chem. 39:153-159.
24. Galzi, J. L., and J. P. Changeux. 1994. Neurotransmitter-gated ion channels as unconventional allosteric proteins. Curr. Opin. Struct. Biol. 4:554-565.
25. Galzi, J. L., A. Devillers-Thiery, N. Hussy, S. Bertrand, J. P. Changeux, and D. Bertrand. 1992. Mutations in the channel domain of a neuronal nicotinic receptor convert ion selectivity from cationic to anionic. Nature. 359:500-505.
26. Gilson, M. K., K. A. Sharp, and B. H. Honig. 1988. Calculating the electrostatic potential of molecules in solution: method and error assessment. J. Comp. Chem. 9:327-335.
27. 3H]chlorpromazine labels homologous residues in the α and δ chains. Biochemistry. 26:2410-2418.
28. Green, M. E., and J. Lewis. 1991. Monte Carlo simulation of the water in a channel with charges. Biophys. J. 59:419-426.
29. Green, M, E., and J. Lu. 1995. Monte-Carlo simulations of the effects of charges on water and ions in a tapered pore. J. Colloid Interface Sci. 171:117-126.
30. Gutman, M., Y. Tsfadia, A. Masad, and E. Nachiel. 1992. Quantitation of physical-chemical properties of the aqueous phase inside the phoE ionic channel. Biochim. Biophys. Acta. 1109:141-148.
31. Guy, H. R., and F. Hucho. 1987. The ion channel of the nicotinic acetylcholine receptor. Trends Neurosci. 10:318-321.
32. Harvey, S. C. 1989. Treatment of electrostatic effects in macromolecular modelling. Proteins Struct. Funct. Genet. 5:78-92.
33. Hucho, F., U. Görne-Tschelnokow, and A. Strecker. 1994. β-Structure in the membrane-spanning part of the nicotinic acetylcholine receptor (or how helical are transmembrane helices?). Trends Biochem. Sci. 19:383-387.
34. Hucho, F., and R. Hilgenfeld. 1989. The selectivity filter of a ligand-gated ion channel. FEBS Lett. 257:17-23.
35. Hucho, F., W. Oberthür, and F. Lottspeich. 1986. The ion channel of the nicotinic acetylcholine receptor is formed by the homologous helices M II of the receptor subunits. FEBS Lett. 205:137-142.
36. Imoto, K., C. Busch, B. Sakmann, M. Mishina, T. Konno, J. Nakai, H. Buyo, Y. Mori, K. Kukuda, and S. Numa. 1988. Rings of negatively charged amino acids determine the acetylcholine receptor channel conductance. Nature. 335:645-648.
37. Karlin, A., and M. H. Akabas. 1995. Toward a structural basis for the function of nicotinic acetylcholine receptors and their cousins. Neuron. 15:1231-1244.
38. Karshikoff, A., V. Spassov, S. W. Cowan, R. Ladenstein, and T. Schirmer. 1994. Electrostatic properties of two porin channels from Escherichia coli. J. Mol. Biol. 240:372-384.
39. Kerr, I. D., D. G. Doak, R. Sankararamakrishnan, J. Breed, and M. S. P. Sansom. 1996. Molecular modelling of staphylococcal δ-toxin ion channels by restrained molecular dynamics. Protein Eng. 9:161-171.
40. Kerr, I. D., R. Sankararamakrishnan, O. S. Smart, and M. S. P. Sansom. 1994. Parallel helix bundles and ion channels: molecular modelling via simulated annealing and restrained molecular dynamics. Biophys. J. 67:1501-1515.
41. Ken, I. D., and M. S. P. Sansom. 1993. Hydrophilic surface maps of α-helical channel-forming peptides. Eur. Biophys. J. 22:269-277.
42. Kienker, P., G. Tomaselli, M. Jurman, and G. Yellen. 1994. Conductance mutations of the nicotinic acetylcholine receptor do not act by a simple electrostatic mechanism. Biophys. J. 66:325-334.
43. Kraulis, P. J. 1991. MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures. J. Appl. Cryst. 24:946-950.
44. Kreusch, A., and G. E. Schulz. 1994. Refined structure of the porin from Rhodobacter blastica. J. Mol Biol. 243:891-905.
45. Labarca, C., M. W. Nowak, L. Tang, P. Deshpande, N. Davidson, and H. Lester. 1995. Leucine residues at the 9 position of the M2 domain in AChR govern EC50 independently and symmetrically. Biophys. J. 68: A233.
46. Leonard, R. J., C. G. Labarca, P. Charnet, N. Davidson, and H. A. Lester. 1988. Evidence that the M2 membrane-spanning region lines the ion channel pore of the nicotinic receptor. Science. 242:1578-1581.
47. Lester, H. 1992. The permeation pathway of neurotransmitter-gated ion channels. Annu. Rev. Biophys. Biomol. Struct. 21:267-292.
48. Montal, M. 1995. Design of molecular function: channels of communication. Annu. Rev. Biophys. Biomol. Struct. 24:31-57.
49. Moore, W. J. 1972. Physical Chemistry. Longman, London.
50. Nicholls, A., and B. Honig. 1992. GRASP Manual. Columbia University, New York.
51. Nilges, M., and A. T. Brünger. 1991. Automated modelling of coiled coils: application to the GCN4 dimerization region. Protein Eng. 4:649-659.
52. Nilges, M., and A. T. Brünger. 1993. Successful prediction of the coiled coil geometry of the GCN4 leucine zipper domain by simulated annealing: comparison to the X ray structure. Proteins Struct. Funct. Genet. 15:133-146.
53. Nutter, T. J., and D. J. Adams. 1995. Monovalent and divalent cation permeability and block of neuronal nicotinic receptor channels in rat parasympathetic ganglia. J Gen. Physiol 105:701-723.
54. Oiki, S., W. Danho, V. Madison, and M. Montai. 1988. M2δ, a candidate for the structure lining the ionic channel of the nicotinic cholinergic receptor. Proc. Natl. Acad. Sci. USA. 85:8703-8707.
55. Oiki, S., V. Madison, and M. Montal. 1990. Bundles of amphipathic transmembrane α-helices as a structural motif for ion conducting channel proteins: studies on sodium channels and acetylcholine receptors. Proteins Struct. Funct. Genet. 8:226-236.
56. Orteils, M. O., and G. G. Lunt. 1994. The transmembrane region of the nicotinic acetylcholine receptor: is it an all-helix bundle? Receptors Channels. 2:53-59.
57. Ortells, M. O., and G. G. Lunt. 1996. A mixed helix-beta-sheet model of the transmembrane region of the nicotinic acetylcholine receptor. Protein Eng. 9:51-59.
58. Peitzsch, R. M., M. Eisenberg, K. A. Sharp, and S. McLaughlin. 1995. Calculations of the electrostatic potential adjacent to model phospholipid bilayers. Biophys. J. 68:729-738.
59. Ripoll, D. R., C. H. Faerman, P. H. Axelsen, I. Silman, and J. L. Sussman, 1993. An electrostatic mechanism for substrate guidance down the aromatic gorge of acetylcholineesterase. Proc. Natl. Acad Sci. USA. 90:5128-5132.
60. Roux, B., and M. Karplus. 1994. Molecular dynamics simulations of the gramicidin channel. Annu. Rev. Biophys. Biomol. Struct. 23:731-761.
61. Sankararamakrishnan, R., and M. S. P. Sansom. 1995a. Modelling packing interactions in parallel helix bundles: pentameric bundles of nicotinic receptor M2 helices. Biochim. Biophys. Acta. 1239:122-132.
62. Sankararamakrishnan, R., and M. S. P. Sansom. 1995b. Structural features of isolated M2 helices of nicotinic receptors. Simulated annealing via molecular dynamics studies. Biophys. Chem. 55:215-230.
63. Sansom, M. S. P. 1995. Twist to open. Curr. Biol. 5:373-375.
64. Sansom, M. S. P., and I. D. Kerr. 1995. Transbilayer pores formed by β-barrels: molecular modelling of pore structures and properties. Biophys. J. 69:1334-1343.
65. Sansom, M. S. P., I. D. Kerr, J. Breed, and R. Sankararamakrishnan. 1996. Water in channel-like cavities: structure and dynamics. Biophys. J. 70:693-702.
66. Sansom, M. S. P., R. Sankararamakrishnan, and I. D. Kerr. 1995a. Modelling membrane proteins using structural restraints. Nature Struct. Biol. 2:624-631.
67. Sansom, M. S. P., H. S. Son, R. Sankararamakrishnan, I. D. Kerr, and J. Breed. 1995b. Seven-helix bundles: molecular modelling via restrained molecular dynamics. Biophys. J. 68:1295-1310.
68. Sharp, K. A., and B. Honig. 1990. Electrostatic interactions in macromolecules: theory and applications. Annu. Rev. Biophys. Biophys. Chem. 19:301-332.
69. Sivilotti, L., and D. Colquhoun. 1995. Acetylcholine receptors: too many channels, too few functions. Science. 269:1681-1682.
70. Smart, O. S., J. M. Goodfellow, and B. A. Wallace. 1993. The pore dimensions of gramicidin A. Biophys. J. 65:2455-2460.
71. Stroud, R. M., M. P. McCarthy, and M. Shuster. 1990. Nicotinic acetylcholine receptor superfamily of ligand gated ion channels. Biochemistry. 29:11009-11023.
72. Treutlein, H. R., M. A. Lemmon, D. M. Engelman, and A. T. Brunger. 1992. The glycophorin A transmembrane domain dimer: sequence specific propensity for a right handed supercoil of helices. Biochemistry. 31:12726-12733.
73. Unwin, N. 1993. Nicotinic acetylcholine receptor at 9 A resolution. J. Mol. Biol. 229:1101-1124.
74. Unwin, N. 1995. Acetylcholine receptor channel imaged in the open state. Nature. 373:37-43.
75. Unwin, N. 1996. Projection structure of the nicotinic acetylcholine receptor: distinct conformations of the a subunits. J. Mol. Biol. 257:586-596.
76. Villarroel, A., S. Herlitze, M. Koenen, and B. Sakmann. 1991. Location of a threonine residue in the a-subunit M2 transmembrane segment that determines the ion flow through the acetylcholine receptor channel. Proc. R. Soc. Lond. B. 243:69-74.
77. Villaroel, A., S. Herlitze, V. Witzemann, M. Koenen, and B. Sakmann. 1992. Asymmetry of the rat acetylcholine receptor subunits in the narrow region of the pore. Proc. R. Soc. Lond. B. 249:317-324.
78. Villaroel, A., and B. Sakmann. 1992. Threonine in the selectivity filter of the acetylcholine receptor channel. Biophys. J. 62:196-205.
79. von Kitzing, E. 1995. Structure modeling of the acetylcholine receptor channel and related ligand gated channels. In Modelling of Biomolecular Structures and Mechanisms. A. Pullman, editor. Dordrecht, Kluwer. 39-57.