1932

Abstract

▪ Abstract 

This article is mostly about the beginnings of the molecular biology of membranes, covering the decade 1964–1974. It is difficult to read (or write) this article because of a sense of déja vu. Most of the material in it is considered commonplace today, having been established experimentally since then. But at the time this work was begun, practically nothing was known about the molecular structure and the mechanisms of the functions of membranes. This situation existed because no membrane proteins of the kind I called integral had as yet been isolated in a pure state, and therefore none had had their amino acid sequence determined. The first integral membrane protein to be so characterized was human erythrocyte glycophorin, in 1978. It was the use of the thermodynamic reasoning that had been developed for the study of water-soluble proteins, together with the information from several key experiments carried out in a number of laboratories during the early decade, that led us to the fluid mosaic model of membrane structure in 1972. Without direct evidence to confirm the model in 1971–1972, my colleagues and I nevertheless had the confidence in it to pursue some of the consequences of the model for a new understanding of many membrane functions, which I present here in some detail. Finally, I discuss two recent high-resolution X-ray crystallographic studies of integral proteins to ask how well the structural and functional proposals that we derived from the fluid mosaic model fit these remarkably detailed X-ray results.

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/content/journals/10.1146/annurev.physiol.66.032902.131835
2004-03-17
2024-05-12
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Literature Cited

  1. Singer SJ. 1.  1971. The molecular organization of biological membranes. In Structure and Function of Biological Membranes ed. LI Rothfield pp. 145–222 New York: Academic [Google Scholar]
  2. Singer SJ, Nicolson GL. 2.  1972. The fluid mosaic model of the structure of cell membranes. Science 175:720–31 [Google Scholar]
  3. Gorter E, Grendel F. 3.  1925. On bimolecular layers of lipoids on the chromocytes of the blood. J. Exp. Med. 41:439–43 [Google Scholar]
  4. Bar KS, Deamer DW, Cornwell DG. 4.  1966. Surface area of human erythrocyte lipids: reinvestigation of experiments on plasma membrane. Science 153:1010–12 [Google Scholar]
  5. Robertson JD. 5.  1964. Unit membranes: a review with recent new studies of experimental alterations and a new subunit structure in synaptic membranes. In Cellular Membranes in Development ed. M Locke pp. 1–81 New York/London: Academic [Google Scholar]
  6. Davson H, Danielli JF. 6.  1952. The Permeability of Natural Membranes London/New York: Cambridge Univ. Press, 2nd ed..
  7. Kauzmann W. 7.  1959. Some factors in the interpretation of protein denaturation. Advan. Protein Chem. 14:1–63 [Google Scholar]
  8. Kendrew JC. 8.  1961. The three-dimensional structure of a protein molecule. Sci. Am. 205:96–111 [Google Scholar]
  9. Perutz MF. 9.  1964. The hemoglobin molecule. Sci. Am. 211:64–76 [Google Scholar]
  10. Klotz IM, Franzen JS. 10.  1962. Hydrogen bonds between model peptide groups in solution. J. Am. Chem. Soc. 84:3461–66 [Google Scholar]
  11. Cohn EJ, Edsall JT. 11.  1943. Proteins, Amino Acids, and Peptides New York: Reinhold [Google Scholar]
  12. Benson AA. 12.  1966. On the orientation of lipids in chloroplast and cell membranes. J. Am. Oil Chem. Soc. 43:265–70 [Google Scholar]
  13. Lenard J, Singer SJ. 13.  1966. Protein conformation in cell membrane preparations as studied by optical rotary dispersion and circular dichroism. Proc. Natl. Acad. Sci. USA 56:1828–35 [Google Scholar]
  14. Wallach DFH, Zahler PH. 14.  1966. Protein conformations in cellular membranes. Proc. Natl. Acad. Sci. USA 56:1552–59 [Google Scholar]
  15. Anderson RGW, Jacobson K. 15.  2002. A role for lipid shells in targeting proteins to caveolae, rafts, and other lipid domains. Science 296:1821–25 [Google Scholar]
  16. Pinto da Silva P, Branton D. 16.  1970. Membrane splitting in freeze etching. J. Cell Biol. 45:598–605 [Google Scholar]
  17. Bretscher M. 17.  1971. A major protein which spans the human erythrocyte membrane. J. Cell Biol. 59:351–57 [Google Scholar]
  18. Lenard J, Singer SJ. 18.  1968. Structure of membranes: reaction of red blood cell membranes with phospholipase C. Science 159:738–39 [Google Scholar]
  19. Singer SJ. 19.  1974. Molecular organization of membranes. Annu. Rev. Biochem. 43:805–33 [Google Scholar]
  20. Ito A, Sato R. 20.  1968. Purification by means of detergents and properties of cytochrome b5 from liver microsomes. J. Biol. Chem. 243:4922–23 [Google Scholar]
  21. Kennedy SJ. 21.  1978. Structures of membrane proteins. J. Membr. Biol. 42:265–79 [Google Scholar]
  22. Weiss MS, Wacker T, Weckesser J, Welte W, Schulz GE. 22.  1990. The three-dimensional structure of porin from Rhodobacter capsulatus at 3 Å resolution. FEBS Lett. 267:268–72 [Google Scholar]
  23. Jap BK. 23.  1989. Molecular design of PhoE porin and its functional consequences. J. Mol. Biol. 205:407–19 [Google Scholar]
  24. Benedetti EL, Emmelot P. 24.  1967. Studies on plasma membranes. IV. The ultrastructural localization and content of sialic acid in plasma membranes isolated from rat liver and hepatoma J. Cell Sci. 2:499–512 [Google Scholar]
  25. Eylar EH, Madoff MA, Brody OV, Oncley JL. 25.  1962. The contribution of sialic acid to the surface charge of the erythrocyte. J. Biol. Chem. 237:1992–2000 [Google Scholar]
  26. Gasic GJ, Berwick L, Sorrentino M. 26.  1968. Positive and negative colloidal iron as cell surface electron stains. Lab Invest. 18:63–71 [Google Scholar]
  27. Nicolson GL, Singer SJ. 27.  1971. Ferritin-conjugated plant agglutinins as specific saccharide stains for electron microscopy: application to saccharides bound to cell membranes. Proc. Natl. Acad. Sci. USA 68:942–45 [Google Scholar]
  28. Nicolson GL, Singer SJ. 28.  1974. The distribution and asymmetry of mammalian cell surface saccharides utilizing ferritin-conjugated plant agglutinins as specific saccharide stains. J. Cell Biol. 60:236–48 [Google Scholar]
  29. Hirano H, Parkhouse B, Nicolson GL, Lennox ES, Singer SJ. 29.  1972. Distribution of saccharide residues on membrane fragments from a myeloma-cell homogenate: its implications for membrane biogenesis. Proc. Natl. Acad. Sci. USA 69:2945–49 [Google Scholar]
  30. Nicolson GL, Masouredis SP, Singer SJ. 30.  1971. Quantitative two-dimensional ultrastructural distribution of Rho (D) antigenic sites on human erythrocyte membranes. Proc. Natl. Acad. Sci. USA 68:1416–20 [Google Scholar]
  31. Nicolson GL, Hyman R, Singer SJ. 31.  1971. The two-dimensional topographic distribution of H-2 histocompatibility alloantigens on mouse red blood cell membranes. J. Cell Biol. 50:905–10 [Google Scholar]
  32. Rothman J, Kennedy EP. 32.  1977. Rapid transmembrane movement of newly synthesized phospholipids during membrane assembly. Proc. Natl. Acad. Sci. USA 74:1821–25 [Google Scholar]
  33. Daleke DL, Lyles JV. 33.  2000. Identification and purification of aminophospholipid flippases. Biochim. Biophys. Acta 1486:108–27 [Google Scholar]
  34. Hubbell WL, McConnell HM. 34.  1968. Spin-label studies of the excitable membranes of nerve and muscle. Proc. Natl. Acad. Sci. USA 61:12–16 [Google Scholar]
  35. Wilkins MHF, Blaurock AE, Engelman DM. 35.  1971. Bilayer structure in membranes. Nat. New Biol. 230:72–76 [Google Scholar]
  36. Melchoir DL, Morowitz HJ, Sturtevant JM, Tsong TY. 36.  1970. Characterization of the plasma membrane of Mycoplasma laidlawii.. VII. Phase transitions of membrane lipids Biochim. Biophys. Acta 219:114–22 [Google Scholar]
  37. Frye CD, Edidin M. 37.  1970. The rapid intermixing of cell surface antigens after formation of mouse-human heterokaryons. J. Cell Sci. 7:319–35 [Google Scholar]
  38. Tokuyasu KT, Schekman R, Singer SJ. 38.  1979. Domains of receptor mobility and endocytosis in the membranes of neonatal human erythrocytes and reticulocytes are deficient in spectrin. J. Cell Biol. 80:481–86 [Google Scholar]
  39. Taylor RB, Duffus WPH, Raff MC, de Petris S. 39.  1971. Redistribution and pinocytosis of lymphocyte surface immunoglobulin molecules induced by anti-immunoglobulin antibody. Nat. New Biol. 233:225–29 [Google Scholar]
  40. Tomita M, Furthmayr H, Marchesi VT. 40.  1978. Primary structure of human erythrocyte glycophorin A. Isolation and characterization of peptides and complete amino acid sequence Biochemistry 17:4756–70 [Google Scholar]
  41. Monod J, Changeux JP, Wyman J. 41.  1963. Allosteric proteins and cellular control systems. J. Mol. Biol. 6:306–29 [Google Scholar]
  42. Schlessinger J, Ullrich A. 42.  1992. Growth factor signaling by receptor tyrosine kinases. Neuron 9:383–91 [Google Scholar]
  43. Vassilatis DK, Hohmann JG, Zeng H, Li F, Ranchalis JE. 43.  et al. 2003. The G protein-coupled receptor repertoires of human and mouse. Proc. Natl. Acad. Sci. USA 100:4903–8 [Google Scholar]
  44. Hur EM, Kim KT. 44.  2002. G protein-coupled receptor signalling and cross-talk. Achieving rapidity and specificity Cell. Signal. 14:397–405 [Google Scholar]
  45. Weill CL, McNamee MG, Karlin A. 45.  1974. Affinity-labeling of purified acetylcholine receptor from Torpedo californica. Biochim. Biophys. Res. Commun. 61:997–1003 [Google Scholar]
  46. Unwin N. 46.  1993. Nicotinic acetylcholine receptor at 9 Å resolution. J. Mol. Biol. 229:1101–24 [Google Scholar]
  47. Unwin N. 47.  1995. Acetylcholine receptor channel imaged in the open state. Nature 373:37–43 [Google Scholar]
  48. Jiang Y, Lee A, Chen J, Cadene M, Chait BT. 48.  et al. 2002. Crystal structure and mechanism of a calcium-gated potassium channel. Nature 417:515–22 [Google Scholar]
  49. Blobel G. 49.  2000. Protein targeting (Nobel Lecture). Chembiochem 1:87–102 [Google Scholar]
  50. Zwaal RFA, Roelofsen B, Colley CM. 50.  1973. Localization of red cell membrane constituents. Biochim. Biophys. Acta 300:159–82 [Google Scholar]
  51. Verkleij AJ, Zwaal RFA, Roelofsen B, Comfurius P, Kastelijn D. 51.  et al. 1973. The asymmetric distribution of phospholipids in the human red cell membrane. A combined study using phospholipases and freeze-etch electron microscopy Biochim. Biophys. Acta 323:178–93 [Google Scholar]
  52. Sheetz MP, Singer SJ. 52.  1974. Biological membranes as bilayer couples. A molecular mechanism of drug-erythrocyte interactions Proc. Natl. Acad. Sci. USA 71:4457–61 [Google Scholar]
  53. Sheetz MP, Singer SJ. 53.  1976. Equilibrium and kinetic effects of drugs on the shapes of human erythrocytes. J. Cell Biol. 70:247–51 [Google Scholar]
  54. Israelachvili J, Marcelja S, Horn R. 54.  1980. Physical principles of membrane organization. Q. Rev. Biophys. 13:121–200 [Google Scholar]
  55. Pearse BMF. 55.  1976. Clathrin: a unique protein associated with the intracellular transfer of membrane by coated vesicles. Proc. Natl. Acad. Sci. USA 73:1255–59 [Google Scholar]
  56. Deisenhofer J, Epp O, Miki K, Huber R, Michel H. 56.  1985. Structure of the protein subunits in the photosynthetic reaction center of Rhodopseudomonas viridis at 3 Å resolution. Nature 318:618–24 [Google Scholar]
  57. Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H. 57.  et al. 2000. Crystal structure of rhodopsin: a G protein-coupled receptor. Science 289:739–45 [Google Scholar]
  58. Okada T, Fujiyoshi Y, Silow M, Navarro J, Landau EM. 58.  et al. 2002. Functional role of internal water molecules in rhodopsin revealed by X-ray crystallography. Proc. Natl. Acad. Sci. USA 99:5982–87 [Google Scholar]
  59. Brandon C, Tooze J. 59.  1991. Introduction to Protein Structure pp. 203–12 New York/London: Garland
  60. Knapp EW, Fischer SF, Zinth W, Sander M, Kaiser W. 60.  et al. 1985. Analysis of optical spectra from single crystals of Rhodopseudomonas viridis reaction centers. Proc. Natl. Acad. Sci. USA 82:8463–67 [Google Scholar]
  61. Ovchinnikov YA. 61.  1982. Rhodopsin and bacteriorhodopsin: structure-function relationships. FEBS Lett. 148:179–91 [Google Scholar]
  62. Dunn RJ, Hackett NR, Huang KS, Jones SS, Khorana HG. 62.  1983. Studies on the light-transducing pigment bacterial rhodopsin. Cold Spring Harbor Symp. Quant. Biol. 48:853–62 [Google Scholar]
  63. Brown M, Ye J, Rawson RB, Goldstein JL. 63.  2000. Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans. Cell 100:391–98 [Google Scholar]
  64. Kyte J, Doolittle RF. 64.  1982. A simple method for displaying the hydropathic character of a protein. J. Mol. Biol. 157:105–32 [Google Scholar]
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