Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1984 Jan;81(1):155–159. doi: 10.1073/pnas.81.1.155

Amphipathic analysis and possible formation of the ion channel in an acetylcholine receptor.

J Finer-Moore, R M Stroud
PMCID: PMC344629  PMID: 6320162

Abstract

Fourier analysis of the hydrophobicities of the acetylcholine receptor subunit sequences reveals regions of amphipathic secondary structure. Prediction of a consensus secondary structure based on this analysis and on an empirical prediction method leads to a testable hypothesis about how the ion channel is formed and might function. Knowledge of the three-dimensional structure of acetylcholine receptors is consistent with features of the model proposed and provides some constraints.

Full text

PDF
159

Selected References

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

  1. Anderson D. J., Blobel G. In vitro synthesis, glycosylation, and membrane insertion of the four subunits of Torpedo acetylcholine receptor. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5598–5602. doi: 10.1073/pnas.78.9.5598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Dwyer T. M., Adams D. J., Hille B. The permeability of the endplate channel to organic cations in frog muscle. J Gen Physiol. 1980 May;75(5):469–492. doi: 10.1085/jgp.75.5.469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. FURUKAWA T., FURUKAWA A. Effects of methyl- and ethyl-derivatives of NH4 on the neuromuscular junction. Jpn J Physiol. 1959 Jun 25;9(2):130–142. doi: 10.2170/jjphysiol.9.130. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Guy H. R. Structural models of the nicotinic acetylcholine receptor and its toxin-binding sites. Cell Mol Neurobiol. 1981 Sep;1(3):231–258. doi: 10.1007/BF00710680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Huang L. Y., Catterall W. A., Ehrenstein G. Selectivity of cations and nonelectrolytes for acetylcholine-activated channels in cultured muscle cells. J Gen Physiol. 1978 Apr;71(4):397–410. doi: 10.1085/jgp.71.4.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kistler J., Stroud R. M., Klymkowsky M. W., Lalancette R. A., Fairclough R. H. Structure and function of an acetylcholine receptor. Biophys J. 1982 Jan;37(1):371–383. doi: 10.1016/S0006-3495(82)84685-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Klymkowsky M. W., Stroud R. M. Immunospecific identification and three-dimensional structure of a membrane-bound acetylcholine receptor from Torpedo californica. J Mol Biol. 1979 Mar 5;128(3):319–334. doi: 10.1016/0022-2836(79)90091-3. [DOI] [PubMed] [Google Scholar]
  11. Kosower E. M. Partial tertiary structure assignment for the acetylcholine receptor on the basis of the hydrophobicity of amino acid sequences and channel location using single group rotation theory. Biochem Biophys Res Commun. 1983 Mar 29;111(3):1022–1026. doi: 10.1016/0006-291x(83)91402-x. [DOI] [PubMed] [Google Scholar]
  12. Kosower E. M. Partial tertiary structure assignments for the beta-, gamma- and delta-subunits of the acetylcholine receptor on the basis of the hydrophobicity of amino acid sequences and channel location using single group rotation theory. FEBS Lett. 1983 May 8;155(2):245–247. doi: 10.1016/0014-5793(82)80613-3. [DOI] [PubMed] [Google Scholar]
  13. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  14. Lewis C. A. Ion-concentration dependence of the reversal potential and the single channel conductance of ion channels at the frog neuromuscular junction. J Physiol. 1979 Jan;286:417–445. doi: 10.1113/jphysiol.1979.sp012629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lewis C. A., Stevens C. F. Acetylcholine receptor channel ionic selectivity: ions experience an aqueous environment. Proc Natl Acad Sci U S A. 1983 Oct;80(19):6110–6113. doi: 10.1073/pnas.80.19.6110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lindstrom J., Merlie J., Yogeeswaran G. Biochemical properties of acteylcholine receptor subunits from Torpedo californica. Biochemistry. 1979 Oct 16;18(21):4465–4470. doi: 10.1021/bi00588a003. [DOI] [PubMed] [Google Scholar]
  17. Maeno T., Edwards C., Anraku M. Permeability of the endplate membrane activated by acetylcholine to some organic cations. J Neurobiol. 1977 Mar;8(2):173–184. doi: 10.1002/neu.480080208. [DOI] [PubMed] [Google Scholar]
  18. McLachlan A. D., Karn J. Periodic features in the amino acid sequence of nematode myosin rod. J Mol Biol. 1983 Mar 15;164(4):605–626. doi: 10.1016/0022-2836(83)90053-0. [DOI] [PubMed] [Google Scholar]
  19. McLachlan A. D., Stewart M. The 14-fold periodicity in alpha-tropomyosin and the interaction with actin. J Mol Biol. 1976 May 15;103(2):271–298. doi: 10.1016/0022-2836(76)90313-2. [DOI] [PubMed] [Google Scholar]
  20. McLachlan A. D. Tests for comparing related amino-acid sequences. Cytochrome c and cytochrome c 551 . J Mol Biol. 1971 Oct 28;61(2):409–424. doi: 10.1016/0022-2836(71)90390-1. [DOI] [PubMed] [Google Scholar]
  21. Merlie J. P., Sebbane R. Acetylcholine receptor subunits transit a precursor pool before acquiring alpha-bungarotoxin binding activity. J Biol Chem. 1981 Apr 25;256(8):3605–3608. [PubMed] [Google Scholar]
  22. Merlie J. P., Sebbane R., Tzartos S., Lindstrom J. Inhibition of glycosylation with tunicamycin blocks assembly of newly synthesized acetylcholine receptor subunits in muscle cells. J Biol Chem. 1982 Mar 10;257(5):2694–2701. [PubMed] [Google Scholar]
  23. 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]
  24. Noda M., Takahashi H., Tanabe T., Toyosato M., Furutani Y., Hirose T., Asai M., Inayama S., Miyata T., Numa S. Primary structure of alpha-subunit precursor of Torpedo californica acetylcholine receptor deduced from cDNA sequence. Nature. 1982 Oct 28;299(5886):793–797. doi: 10.1038/299793a0. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Noda M., Takahashi H., Tanabe T., Toyosato M., Kikyotani S., Hirose T., Asai M., Takashima H., Inayama S., Miyata T. Primary structures of beta- and delta-subunit precursors of Torpedo californica acetylcholine receptor deduced from cDNA sequences. Nature. 1983 Jan 20;301(5897):251–255. doi: 10.1038/301251a0. [DOI] [PubMed] [Google Scholar]
  27. Raftery M. A., Hunkapiller M. W., Strader C. D., Hood L. E. Acetylcholine receptor: complex of homologous subunits. Science. 1980 Jun 27;208(4451):1454–1456. doi: 10.1126/science.7384786. [DOI] [PubMed] [Google Scholar]
  28. Reynolds J. A., Karlin A. Molecular weight in detergent solution of acetylcholine receptor from Torpedo californica. Biochemistry. 1978 May 30;17(11):2035–2038. doi: 10.1021/bi00604a001. [DOI] [PubMed] [Google Scholar]
  29. Richardson J. S., Getzoff E. D., Richardson D. C. The beta bulge: a common small unit of nonrepetitive protein structure. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2574–2578. doi: 10.1073/pnas.75.6.2574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Richardson J. S. beta-Sheet topology and the relatedness of proteins. Nature. 1977 Aug 11;268(5620):495–500. doi: 10.1038/268495a0. [DOI] [PubMed] [Google Scholar]
  31. Ross M. J., Klymkowsky M. W., Agard D. A., Stroud R. M. Structural studies of a membrane-bound acetylcholine receptor from Torpedo californica. J Mol Biol. 1977 Nov;116(4):635–659. doi: 10.1016/0022-2836(77)90264-9. [DOI] [PubMed] [Google Scholar]
  32. Sabatini D. D., Kreibich G., Morimoto T., Adesnik M. Mechanisms for the incorporation of proteins in membranes and organelles. J Cell Biol. 1982 Jan;92(1):1–22. doi: 10.1083/jcb.92.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Salemme F. R., Weatherford D. W. Conformational and geometrical properties of beta-sheets in proteins. II. Antiparallel and mixed beta-sheets. J Mol Biol. 1981 Feb 15;146(1):119–141. doi: 10.1016/0022-2836(81)90369-7. [DOI] [PubMed] [Google Scholar]
  34. Sumikawa K., Houghton M., Smith J. C., Bell L., Richards B. M., Barnard E. A. The molecular cloning and characterisation of cDNA coding for the alpha subunit of the acetylcholine receptor. Nucleic Acids Res. 1982 Oct 11;10(19):5809–5822. doi: 10.1093/nar/10.19.5809. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES