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. 1999 May;76(5):2329–2345. doi: 10.1016/S0006-3495(99)77390-X

Improved secondary structure predictions for a nicotinic receptor subunit: incorporation of solvent accessibility and experimental data into a two-dimensional representation.

N Le Novère 1, P J Corringer 1, J P Changeux 1
PMCID: PMC1300207  PMID: 10233052

Abstract

Abstract A refined prediction of the nicotinic acetylcholine receptor (nAChR) subunits' secondary structure was computed with third-generation algorithms. The four selected programs, PHD, Predator, DSC, and NNSSP, based on different prediction approaches, were applied to each sequence of an alignment of nAChR and 5-HT3 receptor subunits, as well as a larger alignment with related subunit sequences from glycine and GABA receptors. A consensus prediction was computed for the nAChR subunits through a "winner takes all" method. By integrating the probabilities obtained with PHD, DSC, and NNSSP, this prediction was filtered in order to eliminate the singletons and to more precisely establish the structure limits (only 4% of the residues were modified). The final consensus secondary structure includes nine alpha-helices (24.2% of the residues, with an average length of 13.9 residues) and 17 beta-strands (22.5% of the residues, with an average length of 6.6 residues). The large extracellular domain is predicted to be mainly composed of beta-strands, with only two helices at the amino-terminal end. The transmembrane segments are predicted to be in a mixed alpha/beta topology (with a predominance of alpha-helices), with no known equivalent in the current protein database. The cytoplasmic domain is predicted to consist of two well-conserved amphipathic helices joined together by an unfolded stretch of variable length and sequence. In general, the segments predicted to occur in a periodic structure correspond to the more conserved regions, as defined by an analysis of sequence conservation per position performed on 152 superfamily members. The solvent accessibility of each residue was predicted from the multiple alignments with PHDacc. Each segment with more than three exposed residues was assumed to be external to the core protein. Overall, these data constitute an envelope of structural constraints. In a subsequent step, experimental data relative to the extracellular portion of the complete receptor were incorporated into the model. This led to a proposed two-dimensional representation of the secondary structure in which the peptide chain of the extracellular domain winds alternatively between the two interfaces of the subunit. Although this representation is not a tertiary structure and does not lead to predictions of specific beta-beta interaction, it should provide a basic framework for further mutagenesis investigations and for fold recognition (threading) searches.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akabas M. H., Karlin A. Identification of acetylcholine receptor channel-lining residues in the M1 segment of the alpha-subunit. Biochemistry. 1995 Oct 3;34(39):12496–12500. doi: 10.1021/bi00039a002. [DOI] [PubMed] [Google Scholar]
  2. Akabas M. H., Kaufmann C., Archdeacon P., Karlin A. Identification of acetylcholine receptor channel-lining residues in the entire M2 segment of the alpha subunit. Neuron. 1994 Oct;13(4):919–927. doi: 10.1016/0896-6273(94)90257-7. [DOI] [PubMed] [Google Scholar]
  3. Basus V. J., Song G., Hawrot E. NMR solution structure of an alpha-bungarotoxin/nicotinic receptor peptide complex. Biochemistry. 1993 Nov 23;32(46):12290–12298. doi: 10.1021/bi00097a004. [DOI] [PubMed] [Google Scholar]
  4. Beroukhim R., Unwin N. Three-dimensional location of the main immunogenic region of the acetylcholine receptor. Neuron. 1995 Aug;15(2):323–331. doi: 10.1016/0896-6273(95)90037-3. [DOI] [PubMed] [Google Scholar]
  5. Biou V., Gibrat J. F., Levin J. M., Robson B., Garnier J. Secondary structure prediction: combination of three different methods. Protein Eng. 1988 Sep;2(3):185–191. doi: 10.1093/protein/2.3.185. [DOI] [PubMed] [Google Scholar]
  6. Blanton M. P., Cohen J. B. Identifying the lipid-protein interface of the Torpedo nicotinic acetylcholine receptor: secondary structure implications. Biochemistry. 1994 Mar 15;33(10):2859–2872. doi: 10.1021/bi00176a016. [DOI] [PubMed] [Google Scholar]
  7. Bormann J., Feigenspan A. GABAC receptors. Trends Neurosci. 1995 Dec;18(12):515–519. doi: 10.1016/0166-2236(95)98370-e. [DOI] [PubMed] [Google Scholar]
  8. Bowie J. U., Lüthy R., Eisenberg D. A method to identify protein sequences that fold into a known three-dimensional structure. Science. 1991 Jul 12;253(5016):164–170. doi: 10.1126/science.1853201. [DOI] [PubMed] [Google Scholar]
  9. Butler D. H., McNamee M. G. FTIR analysis of nicotinic acetylcholine receptor secondary structure in reconstituted membranes. Biochim Biophys Acta. 1993 Jul 25;1150(1):17–24. doi: 10.1016/0005-2736(93)90116-h. [DOI] [PubMed] [Google Scholar]
  10. Béchade C., Sur C., Triller A. The inhibitory neuronal glycine receptor. Bioessays. 1994 Oct;16(10):735–744. doi: 10.1002/bies.950161008. [DOI] [PubMed] [Google Scholar]
  11. Cartaud J., Benedetti E. L., Cohen J. B., Meunier J. C., Changeux J. P. Presence of a lattice structure in membrane fragments rich in nicotinic receptor protein from the electric organ of Torpedo marmorata. FEBS Lett. 1973 Jun 15;33(1):109–113. doi: 10.1016/0014-5793(73)80171-1. [DOI] [PubMed] [Google Scholar]
  12. Changeux J. P., Edelstein S. J. Allosteric receptors after 30 years. Neuron. 1998 Nov;21(5):959–980. doi: 10.1016/s0896-6273(00)80616-9. [DOI] [PubMed] [Google Scholar]
  13. Chiara D. C., Cohen J. B. Identification of amino acids contributing to high and low affinity d-tubocurarine sites in the Torpedo nicotinic acetylcholine receptor. J Biol Chem. 1997 Dec 26;272(52):32940–32950. doi: 10.1074/jbc.272.52.32940. [DOI] [PubMed] [Google Scholar]
  14. Chothia C., Lesk A. M. The relation between the divergence of sequence and structure in proteins. EMBO J. 1986 Apr;5(4):823–826. doi: 10.1002/j.1460-2075.1986.tb04288.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Chou P. Y., Fasman G. D. Prediction of the secondary structure of proteins from their amino acid sequence. Adv Enzymol Relat Areas Mol Biol. 1978;47:45–148. doi: 10.1002/9780470122921.ch2. [DOI] [PubMed] [Google Scholar]
  16. Claudio T., Ballivet M., Patrick J., Heinemann S. Nucleotide and deduced amino acid sequences of Torpedo californica acetylcholine receptor gamma subunit. Proc Natl Acad Sci U S A. 1983 Feb;80(4):1111–1115. doi: 10.1073/pnas.80.4.1111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Cockcroft V. B., Osguthorpe D. J., Barnard E. A., Friday A. E., Lunt G. G. Ligand-gated ion channels. Homology and diversity. Mol Neurobiol. 1990 Fall-Winter;4(3-4):129–169. doi: 10.1007/BF02780338. [DOI] [PubMed] [Google Scholar]
  18. Corringer P. J., Bertrand S., Bohler S., Edelstein S. J., Changeux J. P., Bertrand D. Critical elements determining diversity in agonist binding and desensitization of neuronal nicotinic acetylcholine receptors. J Neurosci. 1998 Jan 15;18(2):648–657. doi: 10.1523/JNEUROSCI.18-02-00648.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Corringer P. J., Galzi J. L., Eiselé J. L., Bertrand S., Changeux J. P., Bertrand D. Identification of a new component of the agonist binding site of the nicotinic alpha 7 homooligomeric receptor. J Biol Chem. 1995 May 19;270(20):11749–11752. doi: 10.1074/jbc.270.20.11749. [DOI] [PubMed] [Google Scholar]
  20. Cserzö M., Wallin E., Simon I., von Heijne G., Elofsson A. Prediction of transmembrane alpha-helices in prokaryotic membrane proteins: the dense alignment surface method. Protein Eng. 1997 Jun;10(6):673–676. doi: 10.1093/protein/10.6.673. [DOI] [PubMed] [Google Scholar]
  21. Czajkowski C., Kaufmann C., Karlin A. Negatively charged amino acid residues in the nicotinic receptor delta subunit that contribute to the binding of acetylcholine. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6285–6289. doi: 10.1073/pnas.90.13.6285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Dennis M., Giraudat J., Kotzyba-Hibert F., Goeldner M., Hirth C., Chang J. Y., Lazure C., Chrétien M., Changeux J. P. Amino acids of the Torpedo marmorata acetylcholine receptor alpha subunit labeled by a photoaffinity ligand for the acetylcholine binding site. Biochemistry. 1988 Apr 5;27(7):2346–2357. doi: 10.1021/bi00407a016. [DOI] [PubMed] [Google Scholar]
  23. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Devillers-Thiery A., Giraudat J., Bentaboulet M., Changeux J. P. Complete mRNA coding sequence of the acetylcholine binding alpha-subunit of Torpedo marmorata acetylcholine receptor: a model for the transmembrane organization of the polypeptide chain. Proc Natl Acad Sci U S A. 1983 Apr;80(7):2067–2071. doi: 10.1073/pnas.80.7.2067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Doyle D. A., Morais Cabral J., Pfuetzner R. A., Kuo A., Gulbis J. M., Cohen S. L., Chait B. T., MacKinnon R. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science. 1998 Apr 3;280(5360):69–77. doi: 10.1126/science.280.5360.69. [DOI] [PubMed] [Google Scholar]
  26. Eiselé J. L., Bertrand S., Galzi J. L., Devillers-Thiéry A., Changeux J. P., Bertrand D. Chimaeric nicotinic-serotonergic receptor combines distinct ligand binding and channel specificities. Nature. 1993 Dec 2;366(6454):479–483. doi: 10.1038/366479a0. [DOI] [PubMed] [Google Scholar]
  27. Finer-Moore J., Stroud R. M. Amphipathic analysis and possible formation of the ion channel in an acetylcholine receptor. Proc Natl Acad Sci U S A. 1984 Jan;81(1):155–159. doi: 10.1073/pnas.81.1.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Flores T. P., Orengo C. A., Moss D. S., Thornton J. M. Comparison of conformational characteristics in structurally similar protein pairs. Protein Sci. 1993 Nov;2(11):1811–1826. doi: 10.1002/pro.5560021104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Frishman D., Argos P. Incorporation of non-local interactions in protein secondary structure prediction from the amino acid sequence. Protein Eng. 1996 Feb;9(2):133–142. doi: 10.1093/protein/9.2.133. [DOI] [PubMed] [Google Scholar]
  30. Frishman D., Argos P. Seventy-five percent accuracy in protein secondary structure prediction. Proteins. 1997 Mar;27(3):329–335. doi: 10.1002/(sici)1097-0134(199703)27:3<329::aid-prot1>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  31. Galzi J. L., Bertrand S., Corringer P. J., Changeux J. P., Bertrand D. Identification of calcium binding sites that regulate potentiation of a neuronal nicotinic acetylcholine receptor. EMBO J. 1996 Nov 1;15(21):5824–5832. [PMC free article] [PubMed] [Google Scholar]
  32. Galzi J. L., Revah F., Black D., Goeldner M., Hirth C., Changeux J. P. Identification of a novel amino acid alpha-tyrosine 93 within the cholinergic ligands-binding sites of the acetylcholine receptor by photoaffinity labeling. Additional evidence for a three-loop model of the cholinergic ligands-binding sites. J Biol Chem. 1990 Jun 25;265(18):10430–10437. [PubMed] [Google Scholar]
  33. Garnier J., Osguthorpe D. J., Robson B. Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins. J Mol Biol. 1978 Mar 25;120(1):97–120. doi: 10.1016/0022-2836(78)90297-8. [DOI] [PubMed] [Google Scholar]
  34. Gibrat J. F., Garnier J., Robson B. Further developments of protein secondary structure prediction using information theory. New parameters and consideration of residue pairs. J Mol Biol. 1987 Dec 5;198(3):425–443. doi: 10.1016/0022-2836(87)90292-0. [DOI] [PubMed] [Google Scholar]
  35. Gready J. E., Ranganathan S., Schofield P. R., Matsuo Y., Nishikawa K. Predicted structure of the extracellular region of ligand-gated ion-channel receptors shows SH2-like and SH3-like domains forming the ligand-binding site. Protein Sci. 1997 May;6(5):983–998. doi: 10.1002/pro.5560060504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Harvey S. C., Luetje C. W. Determinants of competitive antagonist sensitivity on neuronal nicotinic receptor beta subunits. J Neurosci. 1996 Jun 15;16(12):3798–3806. doi: 10.1523/JNEUROSCI.16-12-03798.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Hirokawa T., Boon-Chieng S., Mitaku S. SOSUI: classification and secondary structure prediction system for membrane proteins. Bioinformatics. 1998;14(4):378–379. doi: 10.1093/bioinformatics/14.4.378. [DOI] [PubMed] [Google Scholar]
  38. Hucho F., Tsetlin V. I., Machold J. The emerging three-dimensional structure of a receptor. The nicotinic acetylcholine receptor. Eur J Biochem. 1996 Aug 1;239(3):539–557. doi: 10.1111/j.1432-1033.1996.0539u.x. [DOI] [PubMed] [Google Scholar]
  39. Kabsch W., Sander C. How good are predictions of protein secondary structure? FEBS Lett. 1983 May 8;155(2):179–182. doi: 10.1016/0014-5793(82)80597-8. [DOI] [PubMed] [Google Scholar]
  40. King R. D., Sternberg M. J. Identification and application of the concepts important for accurate and reliable protein secondary structure prediction. Protein Sci. 1996 Nov;5(11):2298–2310. doi: 10.1002/pro.5560051116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Kistler J., Stroud R. M. Crystalline arrays of membrane-bound acetylcholine receptor. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3678–3682. doi: 10.1073/pnas.78.6.3678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Lal R., Yu L. Atomic force microscopy of cloned nicotinic acetylcholine receptor expressed in Xenopus oocytes. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7280–7284. doi: 10.1073/pnas.90.15.7280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Langosch D., Thomas L., Betz H. Conserved quaternary structure of ligand-gated ion channels: the postsynaptic glycine receptor is a pentamer. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7394–7398. doi: 10.1073/pnas.85.19.7394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Le Novère N., Changeux J. P. Molecular evolution of the nicotinic acetylcholine receptor: an example of multigene family in excitable cells. J Mol Evol. 1995 Feb;40(2):155–172. doi: 10.1007/BF00167110. [DOI] [PubMed] [Google Scholar]
  45. Levin J. M., Robson B., Garnier J. An algorithm for secondary structure determination in proteins based on sequence similarity. FEBS Lett. 1986 Sep 15;205(2):303–308. doi: 10.1016/0014-5793(86)80917-6. [DOI] [PubMed] [Google Scholar]
  46. MONOD J., WYMAN J., CHANGEUX J. P. ON THE NATURE OF ALLOSTERIC TRANSITIONS: A PLAUSIBLE MODEL. J Mol Biol. 1965 May;12:88–118. doi: 10.1016/s0022-2836(65)80285-6. [DOI] [PubMed] [Google Scholar]
  47. Macdonald R. L., Olsen R. W. GABAA receptor channels. Annu Rev Neurosci. 1994;17:569–602. doi: 10.1146/annurev.ne.17.030194.003033. [DOI] [PubMed] [Google Scholar]
  48. Machold J., Weise C., Utkin Y., Tsetlin V., Hucho F. The handedness of the subunit arrangement of the nicotinic acetylcholine receptor from Torpedo californica. Eur J Biochem. 1995 Dec 1;234(2):427–430. doi: 10.1111/j.1432-1033.1995.427_b.x. [DOI] [PubMed] [Google Scholar]
  49. Marchler-Bauer A., Levitt M., Bryant S. H. A retrospective analysis of CASP2 threading predictions. Proteins. 1997;Suppl 1:83–91. doi: 10.1002/(sici)1097-0134(1997)1+<83::aid-prot12>3.3.co;2-2. [DOI] [PubMed] [Google Scholar]
  50. Moore W. M., Holladay L. A., Puett D., Brady R. N. On the conformation of the acetylcholine receptor protein from Torpedo nobiliana. FEBS Lett. 1974 Sep 1;45(1):145–149. doi: 10.1016/0014-5793(74)80832-x. [DOI] [PubMed] [Google Scholar]
  51. Méthot N., McCarthy M. P., Baenziger J. E. Secondary structure of the nicotinic acetylcholine receptor: implications for structural models of a ligand-gated ion channel. Biochemistry. 1994 Jun 21;33(24):7709–7717. doi: 10.1021/bi00190a026. [DOI] [PubMed] [Google Scholar]
  52. Nayeem N., Green T. P., Martin I. L., Barnard E. A. Quaternary structure of the native GABAA receptor determined by electron microscopic image analysis. J Neurochem. 1994 Feb;62(2):815–818. doi: 10.1046/j.1471-4159.1994.62020815.x. [DOI] [PubMed] [Google Scholar]
  53. Nef P., Oneyser C., Alliod C., Couturier S., Ballivet M. Genes expressed in the brain define three distinct neuronal nicotinic acetylcholine receptors. EMBO J. 1988 Mar;7(3):595–601. doi: 10.1002/j.1460-2075.1988.tb02852.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Nishikawa K. Assessment of secondary-structure prediction of proteins. Comparison of computerized Chou-Fasman method with others. Biochim Biophys Acta. 1983 Oct 28;748(2):285–299. doi: 10.1016/0167-4838(83)90306-0. [DOI] [PubMed] [Google Scholar]
  55. Nishikawa K., Ooi T. Amino acid sequence homology applied to the prediction of protein secondary structures, and joint prediction with existing methods. Biochim Biophys Acta. 1986 May 12;871(1):45–54. doi: 10.1016/0167-4838(86)90131-7. [DOI] [PubMed] [Google Scholar]
  56. Noda M., Takahashi H., Tanabe T., Toyosato M., Kikyotani S., Furutani Y., Hirose T., Takashima H., Inayama S., Miyata T. Structural homology of Torpedo californica acetylcholine receptor subunits. Nature. 1983 Apr 7;302(5908):528–532. doi: 10.1038/302528a0. [DOI] [PubMed] [Google Scholar]
  57. Ortells M. O., Lunt G. G. A mixed helix-beta-sheet model of the transmembrane region of the nicotinic acetylcholine receptor. Protein Eng. 1996 Jan;9(1):51–59. doi: 10.1093/protein/9.1.51. [DOI] [PubMed] [Google Scholar]
  58. Ortells M. O., Lunt G. G. Evolutionary history of the ligand-gated ion-channel superfamily of receptors. Trends Neurosci. 1995 Mar;18(3):121–127. doi: 10.1016/0166-2236(95)93887-4. [DOI] [PubMed] [Google Scholar]
  59. Ortells M. O. Prediction of the secondary structure of the nicotinic acetylcholine receptor nontransmembrane regions. Proteins. 1997 Nov;29(3):391–398. [PubMed] [Google Scholar]
  60. Paas Y. The macro- and microarchitectures of the ligand-binding domain of glutamate receptors. Trends Neurosci. 1998 Mar;21(3):117–125. doi: 10.1016/s0166-2236(97)01184-3. [DOI] [PubMed] [Google Scholar]
  61. Popot J. L., Changeux J. P. Nicotinic receptor of acetylcholine: structure of an oligomeric integral membrane protein. Physiol Rev. 1984 Oct;64(4):1162–1239. doi: 10.1152/physrev.1984.64.4.1162. [DOI] [PubMed] [Google Scholar]
  62. Prince R. J., Sine S. M. Molecular dissection of subunit interfaces in the acetylcholine receptor. Identification of residues that determine agonist selectivity. J Biol Chem. 1996 Oct 18;271(42):25770–25777. doi: 10.1074/jbc.271.42.25770. [DOI] [PubMed] [Google Scholar]
  63. Revah F., Galzi J. L., Giraudat J., Haumont P. Y., Lederer F., Changeux J. P. The noncompetitive blocker [3H]chlorpromazine labels three amino acids of the acetylcholine receptor gamma subunit: implications for the alpha-helical organization of regions MII and for the structure of the ion channel. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4675–4679. doi: 10.1073/pnas.87.12.4675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Rost B. Better 1D predictions by experts with machines. Proteins. 1997;Suppl 1:192–197. doi: 10.1002/(sici)1097-0134(1997)1+<192::aid-prot25>3.3.co;2-y. [DOI] [PubMed] [Google Scholar]
  65. Rost B., Casadio R., Fariselli P. Refining neural network predictions for helical transmembrane proteins by dynamic programming. Proc Int Conf Intell Syst Mol Biol. 1996;4:192–200. [PubMed] [Google Scholar]
  66. Rost B., Casadio R., Fariselli P., Sander C. Transmembrane helices predicted at 95% accuracy. Protein Sci. 1995 Mar;4(3):521–533. doi: 10.1002/pro.5560040318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Rost B., Sander C. Bridging the protein sequence-structure gap by structure predictions. Annu Rev Biophys Biomol Struct. 1996;25:113–136. doi: 10.1146/annurev.bb.25.060196.000553. [DOI] [PubMed] [Google Scholar]
  68. Rost B., Sander C. Combining evolutionary information and neural networks to predict protein secondary structure. Proteins. 1994 May;19(1):55–72. doi: 10.1002/prot.340190108. [DOI] [PubMed] [Google Scholar]
  69. Rost B., Sander C. Conservation and prediction of solvent accessibility in protein families. Proteins. 1994 Nov;20(3):216–226. doi: 10.1002/prot.340200303. [DOI] [PubMed] [Google Scholar]
  70. Rost B., Sander C. Improved prediction of protein secondary structure by use of sequence profiles and neural networks. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7558–7562. doi: 10.1073/pnas.90.16.7558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Rost B., Sander C. Prediction of protein secondary structure at better than 70% accuracy. J Mol Biol. 1993 Jul 20;232(2):584–599. doi: 10.1006/jmbi.1993.1413. [DOI] [PubMed] [Google Scholar]
  72. Russell R. B., Barton G. J. The limits of protein secondary structure prediction accuracy from multiple sequence alignment. J Mol Biol. 1993 Dec 20;234(4):951–957. doi: 10.1006/jmbi.1993.1649. [DOI] [PubMed] [Google Scholar]
  73. Salamov A. A., Solovyev V. V. Prediction of protein secondary structure by combining nearest-neighbor algorithms and multiple sequence alignments. J Mol Biol. 1995 Mar 17;247(1):11–15. doi: 10.1006/jmbi.1994.0116. [DOI] [PubMed] [Google Scholar]
  74. Sander C., Schneider R. Database of homology-derived protein structures and the structural meaning of sequence alignment. Proteins. 1991;9(1):56–68. doi: 10.1002/prot.340090107. [DOI] [PubMed] [Google Scholar]
  75. Schmieden V., Kuhse J., Betz H. Agonist pharmacology of neonatal and adult glycine receptor alpha subunits: identification of amino acid residues involved in taurine activation. EMBO J. 1992 Jun;11(6):2025–2032. doi: 10.1002/j.1460-2075.1992.tb05259.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Sine S. M., Kreienkamp H. J., Bren N., Maeda R., Taylor P. Molecular dissection of subunit interfaces in the acetylcholine receptor: identification of determinants of alpha-conotoxin M1 selectivity. Neuron. 1995 Jul;15(1):205–211. doi: 10.1016/0896-6273(95)90077-2. [DOI] [PubMed] [Google Scholar]
  77. Sixma T. K., Kalk K. H., van Zanten B. A., Dauter Z., Kingma J., Witholt B., Hol W. G. Refined structure of Escherichia coli heat-labile enterotoxin, a close relative of cholera toxin. J Mol Biol. 1993 Apr 5;230(3):890–918. doi: 10.1006/jmbi.1993.1209. [DOI] [PubMed] [Google Scholar]
  78. Thompson J. D., Gibson T. J., Plewniak F., Jeanmougin F., Higgins D. G. The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res. 1997 Dec 15;25(24):4876–4882. doi: 10.1093/nar/25.24.4876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Toyoshima C., Unwin N. Ion channel of acetylcholine receptor reconstructed from images of postsynaptic membranes. Nature. 1988 Nov 17;336(6196):247–250. doi: 10.1038/336247a0. [DOI] [PubMed] [Google Scholar]
  80. Toyoshima C., Unwin N. Three-dimensional structure of the acetylcholine receptor by cryoelectron microscopy and helical image reconstruction. J Cell Biol. 1990 Dec;111(6 Pt 1):2623–2635. doi: 10.1083/jcb.111.6.2623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Tsigelny I., Sugiyama N., Sine S. M., Taylor P. A model of the nicotinic receptor extracellular domain based on sequence identity and residue location. Biophys J. 1997 Jul;73(1):52–66. doi: 10.1016/S0006-3495(97)78047-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Tzartos S. J., Loutrari H. V., Tang F., Kokla A., Walgrave S. L., Milius R. P., Conti-Tronconi B. M. Main immunogenic region of Torpedo electroplax and human muscle acetylcholine receptor: localization and microheterogeneity revealed by the use of synthetic peptides. J Neurochem. 1990 Jan;54(1):51–61. doi: 10.1111/j.1471-4159.1990.tb13282.x. [DOI] [PubMed] [Google Scholar]
  83. Unwin N. Neurotransmitter action: opening of ligand-gated ion channels. Cell. 1993 Jan;72 (Suppl):31–41. doi: 10.1016/s0092-8674(05)80026-1. [DOI] [PubMed] [Google Scholar]
  84. Unwin N. Nicotinic acetylcholine receptor at 9 A resolution. J Mol Biol. 1993 Feb 20;229(4):1101–1124. doi: 10.1006/jmbi.1993.1107. [DOI] [PubMed] [Google Scholar]
  85. Unwin N. Projection structure of the nicotinic acetylcholine receptor: distinct conformations of the alpha subunits. J Mol Biol. 1996 Apr 5;257(3):586–596. doi: 10.1006/jmbi.1996.0187. [DOI] [PubMed] [Google Scholar]
  86. Vandenberg R. J., French C. R., Barry P. H., Shine J., Schofield P. R. Antagonism of ligand-gated ion channel receptors: two domains of the glycine receptor alpha subunit form the strychnine-binding site. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1765–1769. doi: 10.1073/pnas.89.5.1765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  87. Watty A., Weise C., Dreger M., Franke P., Hucho F. The accessible surface of the nicotinic acetylcholine receptor. Identification by chemical modification and cross-linking with 14C-dimethyl suberimidate. Eur J Biochem. 1998 Mar 1;252(2):222–228. doi: 10.1046/j.1432-1327.1998.2520222.x. [DOI] [PubMed] [Google Scholar]
  88. Wells G. B., Anand R., Wang F., Lindstrom J. Water-soluble nicotinic acetylcholine receptor formed by alpha7 subunit extracellular domains. J Biol Chem. 1998 Jan 9;273(2):964–973. doi: 10.1074/jbc.273.2.964. [DOI] [PubMed] [Google Scholar]
  89. West A. P., Jr, Bjorkman P. J., Dougherty D. A., Lester H. A. Expression and circular dichroism studies of the extracellular domain of the alpha subunit of the nicotinic acetylcholine receptor. J Biol Chem. 1997 Oct 10;272(41):25468–25473. doi: 10.1074/jbc.272.41.25468. [DOI] [PubMed] [Google Scholar]
  90. Wilson G. G., Karlin A. The location of the gate in the acetylcholine receptor channel. Neuron. 1998 Jun;20(6):1269–1281. doi: 10.1016/s0896-6273(00)80506-1. [DOI] [PubMed] [Google Scholar]
  91. Yager P., Chang E. L., Williams R. W., Dalziel A. W. The secondary structure of acetylcholine receptor reconstituted in a single lipid component as determined by Raman spectroscopy. Biophys J. 1984 Jan;45(1):26–28. doi: 10.1016/S0006-3495(84)84095-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  92. Yi T. M., Lander E. S. Protein secondary structure prediction using nearest-neighbor methods. J Mol Biol. 1993 Aug 20;232(4):1117–1129. doi: 10.1006/jmbi.1993.1464. [DOI] [PubMed] [Google Scholar]
  93. Yu X. M., Hall Z. W. A sequence in the main cytoplasmic loop of the alpha subunit is required for assembly of mouse muscle nicotinic acetylcholine receptor. Neuron. 1994 Jul;13(1):247–255. doi: 10.1016/0896-6273(94)90473-1. [DOI] [PubMed] [Google Scholar]
  94. Zhang X., Mesirov J. P., Waltz D. L. Hybrid system for protein secondary structure prediction. J Mol Biol. 1992 Jun 20;225(4):1049–1063. doi: 10.1016/0022-2836(92)90104-r. [DOI] [PubMed] [Google Scholar]
  95. von Heijne G. Membrane protein structure prediction. Hydrophobicity analysis and the positive-inside rule. J Mol Biol. 1992 May 20;225(2):487–494. doi: 10.1016/0022-2836(92)90934-c. [DOI] [PubMed] [Google Scholar]

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