Journal of Biosciences

, Volume 6, Issue 4, pp 357–377 | Cite as

Structural mobility and transformations in globular proteins

  • M. Vijayan
  • Dinakar M. Salunke


Although globular proteins are endowed with well defined three-dimensional structures, they exhibit substantial mobility within the framework of the given three-dimensional structure. The different types of mobility found in proteins by and large correspond to the different levels of organisational hierarchy in protein architecture. They are of considerable structural and functional significance, and can be broadly classified into (a) thermal and conformational fluctuations, (b) segmental mobility, (c) interdomain mobility and (d) intersubunit mobility. Protein crystallographic studies has provided a wealth of information on all of them. The temperature factors derived from X-ray diffraction studies provide a measure of atomic displacements caused by thermal and conformational fluctuations. The variation of displacement along the polypeptide chain have provided functionally significant information on the flexibility of different regions of the molecule in proteins such as myoglobin, lysozyme and prealbumin. Segmental mobility often involves the movement of a region or a segment of a molecule with respect to the rest, as in the transition between the apo and the holo structures of lactate dehydrogenase. It may also involve rigidification of a disordered region of the molecule as in the activation of the zymogens of serine proteases. Transitions between the apo and the holo structures of alcohol dehydrogenase, and between the free and the sugar bound forms of hexokinase, are good examples of interdomain mobility caused by hinge-bending. The capability of different domains to move semi-independently contributes greatly to the versatility of immunoglobulin molecules. Interdomain mobility in citrate synthase appears to be more complex and its study has led to an alternative description of domain closure. The classical and the most thoroughly studied case of intersubunit mobility is that in haemoglobin. The stereochemical mechanism of the action of this allosteric protein clearly brings out the functional subtilities that could be achieved through intersubunit movements. In addition to ligand binding and activation, environmental changes also often cause structural transformations. The reversible transformation between 2 Zn insulin and 4 Zn insulin is caused by changes in the ionic strength of the medium. Adenylate Kinase provides a good example for functionally significant reversible conformational transitions induced by variation in pH. Available evidences indicate that reversible structural transformations in proteins could also be caused by changes in the aqueous environment, including those in the amount of water surrounding protein molecules.


Globular proteins conformational mobility structural transformations protein crystallography 


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  1. Adams, M. J., Blundell, T. L., Dodson, E. J., Dodson, G. G., Vijayan, M, Baker, E. N., Harding, M. M., Hodgkin, D. G, Rimmer, B. and Sheat, S. (1969)Nature (London),224, 491.CrossRefGoogle Scholar
  2. Adams, M. J., Ford, G. C, Liljas, A. and Rossmann, M. G. (1973)Biochem. Biophys. Res. Commun.,53, 46.PubMedCrossRefGoogle Scholar
  3. Amzel, L. M. and Poljack, R. (1979)J. Ann. Rev. Biochem.,48, 961.CrossRefGoogle Scholar
  4. Anderson, C. M., Stenkamp, R. E. and Steitz, T. A. (1978)J. Mol. Biol.,123, 15.PubMedCrossRefGoogle Scholar
  5. Artymiuk, P. J., Blake, C. C. F., Grace, D. E. P., Oatley, S. J., Phillips, D. C. and Sternberg, M. J. E. (1979)Nature (London),280, 563.CrossRefGoogle Scholar
  6. Baker, L. J., Hansen, A. M. F., Bhaskara Rao, P., Bryan, W. P. (1983)Biopolymers,22, 1637.PubMedCrossRefGoogle Scholar
  7. Baldwin, J. M. (1975)Prog. Biophys. Mol. Biol.,29, 225.PubMedCrossRefGoogle Scholar
  8. Baldwin, J. and Chothia, C. (1979)J. Mol. Biol.,129, 175.PubMedCrossRefGoogle Scholar
  9. Bennett, W. S. Jr. and Steitz, T. A. (1980)a)J. Mol. Biol.,140, 183.PubMedCrossRefGoogle Scholar
  10. Bennett, W. S. Jr. and Steitz, T. A. (1980)b)J. Mol. Biol.,140, 211.PubMedCrossRefGoogle Scholar
  11. Bentley, G., Dodson, E., Dodson, G., Hodgkin, D. and Mercola, D. (1976)Nature (London),261, 166.CrossRefGoogle Scholar
  12. Bentley, G., Dodson, G. and Levitova, A. (1978)J. Mol. Biol.,126, 871.PubMedCrossRefGoogle Scholar
  13. Blake, C. C. F. and Oatley, S. J. (1982) inConformation in Biology (eds. R. Srinivasan and R. H. Sarma) (New York: Adenine Press), p. 29.Google Scholar
  14. Bloomer, A. C, Champness, J. N., Bricogne, G., Staden, R. and Klug, A. (1978)Nature (London),276, 362.CrossRefGoogle Scholar
  15. Blow, D. M. (1978) inMolecular Interactions and Activity in Proteins, Ciba Foundation Symposium-60 (New Ser.), (Amsterdam: Excerpta Medica and New York: North-Holland Inc.) p. 55.Google Scholar
  16. Blundell, T. L., Cutfield, J. F., Cutfield, S. M., Dodson, E. J., Dodson, G. G., Hodgkin, D. C, Mercola, D. A. and Vijayan, M. (1971)Nature (London),231, 506.CrossRefGoogle Scholar
  17. Blundell, T., Lindley, P., Miller, L., Moss, D., Slingsby, C., Tickle, I., Turnell, B. and Wistow, B. (1981)Nature (London),289, 771.CrossRefGoogle Scholar
  18. Bode, W., Schwager, P. and Huber, R. (1978)J. Mol. Biol.,118, 99.PubMedCrossRefGoogle Scholar
  19. Bolton, W., Cox, J. M. and Perutz, M. F. (1968)J. Mol. Biol.,33, 283.PubMedCrossRefGoogle Scholar
  20. Boyes-Watson, J., Davidson, E. and Perutz, M. F. (1947)Proc. R. Soc. (London),A191, 83.Google Scholar
  21. Bragg, L. and Perutz, M. F. (1952)Proc. R. Soc. (London),A213, 425.Google Scholar
  22. Branden, C. I., Jornvall, H, Eklund, H. and Furugren, B. (1975) inThe Enzymes (ed. P. D. Boyer) 3rd edition, Vol. 11, p. 103.Google Scholar
  23. Careri, G., Grotton, E., Yong, P. H. and Rupley, J. A. (1980)Nature (London),284, 572.CrossRefGoogle Scholar
  24. Case, D. A. and Karplus, M. (1979)J. Mol. Biol. 132, 343.PubMedCrossRefGoogle Scholar
  25. Davies, D. R., Padlan, E. A. and Segal, D. M. (1975)Ann. Rev. Biochem.,44, 639.PubMedCrossRefGoogle Scholar
  26. Dijkstra, B. W., VanNes, G. J. H., Kalk, K. H., Brandenburg, N. P., Hol, W. G. J. and Drenth, J. (1982)Acta Crystallogr.,B38, 793.Google Scholar
  27. Drenth, J., Jansonius, N., Koekoek, R., Swen, H. and Wolthers, B. (1968)Nature (London),218, 929.CrossRefGoogle Scholar
  28. Eftink, M. R. and Ghiron, C. A. (1975)Proc. Nat. Acad. Sci. USA,72, 3290.PubMedCrossRefGoogle Scholar
  29. Eklund, H., Nordstrom, B., Zeppezauer, E., Sodurlund, G., Ohlsonn, I., Boiwe, T., Soderberg, B. O., Tapia, O., Branden, C. I. and Akesson, A. (1976)J. Mol. Biol.,102, 27.PubMedCrossRefGoogle Scholar
  30. Eklund, H., Samama, J. P., Wallen, L., Branden, C. I., Akesson, A. and Jones, T. A. (1981)J. Mol. Biol.,146, 561.PubMedCrossRefGoogle Scholar
  31. Fehlhammer, H., Bode, W. and Huber, R. (1977)J. Mol. Biol.,111, 415.PubMedCrossRefGoogle Scholar
  32. Frauenfelder, H., Petsko, G. A. and Tsernoglou, D. (1979)Nature (London),280, 558.CrossRefGoogle Scholar
  33. Freer, S. T., Kraut, J., Robertus, J. D., Wright, H. T. and Xuang, Ng. H. (1970)Biochemistry,9, 1997.PubMedCrossRefGoogle Scholar
  34. Gelin, B. R., Lee, A. W. M. and Karplus, M. (1983)J. Mol. Biol.,171, 489.PubMedCrossRefGoogle Scholar
  35. Gurd, F. R. N. and Rothgeb, T. M. (1979)Adv. Protein Chem.,33, 73.PubMedGoogle Scholar
  36. Hartmann, H., Parak, F., Steigemann, W., Petsko, G. A., Ringe Ponzi, D., Frauenfelder, H. (1982)Proc. Natl. Acad. Sci. USA,79, 4967.PubMedCrossRefGoogle Scholar
  37. Holbrook, J. J., Liljas, A., Steindel, S. J. and Rossmann, M. G. (1975) inThe Enzymes (ed. P. D. Boyer) 3rd edition, Vol. 11, p. 191.Google Scholar
  38. Huber, R. and Bennett, W. S. (1983)Biopolymers,22, 261.PubMedCrossRefGoogle Scholar
  39. Huber, R. and Bode, W. (1978)Acc. Chem. Res.,11, 114.CrossRefGoogle Scholar
  40. Huber, R., Kukla, D., Bode, W., Schwager, P., Bartels, K., Deisenhofer, J. and Steigemann, W. (1974)J. Mol. Biol.,89, 73.PubMedCrossRefGoogle Scholar
  41. Huxley, H. E. and Kendrew, J. C. (1953)Acta Crystallogr. 6, 76.CrossRefGoogle Scholar
  42. James, M. N. G., Seilecki, A., Salituro, F., Rich, D. H. and Hofmann, T. (1982)Proc. Natl. Acad. Sci. USA,79, 6137.PubMedCrossRefGoogle Scholar
  43. Janin, J. and Wodak, S. J. (1983)Prog. Biophys. Mol. Biol.,42, 21.PubMedCrossRefGoogle Scholar
  44. Kassiakoff, A. A. (1982)Nature (London),296, 713.CrossRefGoogle Scholar
  45. Kuntz, Jr. I. D. and Kauzmann, W. (1974)Adv. Protein Chem.,28, 239.PubMedGoogle Scholar
  46. Ladner, J. E., Kitchell, J. P., Honzotko, H. M. Ke., Volz, K. W., Kolb, A. J., Ladner, R. C. and Lipscomb, W. N. (1982)Proc. Natl Acad. Sci. USA,79, 3125.PubMedCrossRefGoogle Scholar
  47. Lakowicz, J. R. and Weber, G. (1973)Biochemistry,12, 4171.PubMedCrossRefGoogle Scholar
  48. Lesk, A. M. and Chothia, C. (1984)J. Mol. Biol.,174, 175.PubMedCrossRefGoogle Scholar
  49. Levitt, M. (1983a)J. Mol. Biol.,168, 595.PubMedCrossRefGoogle Scholar
  50. Levitt, M. (1983b)J. Mol. Biol.,168, 621.PubMedCrossRefGoogle Scholar
  51. McCammon, J. A. and Karplus, M. (1983)Acc. Chem. Res. 16, 187.CrossRefGoogle Scholar
  52. McDonald, R. C, Steitz, T. A. and Engelman, D. M. (1979)Biochemistry,18, 338.PubMedCrossRefGoogle Scholar
  53. Monod, J., Wyman, J. and Changeux, J. F. (1965)J. Mol. Biol.,12, 88.PubMedGoogle Scholar
  54. Muirhead, H., Cox, J. M., Mazzarella, L. and Perutz, M. F. (1967)J. Mol. Biol.,28, 117.PubMedCrossRefGoogle Scholar
  55. Northrup, S. H., pear, M. R., McCammon, J. A. and Karplus, M. (1981)J. Mol. Biol,153, 1087.PubMedCrossRefGoogle Scholar
  56. Northrup, S. H., Pear,.. R., McCammon, J. A., Karplus, M. and Takano, T. (1980)Nature (London),287, 659.CrossRefGoogle Scholar
  57. Pai, E. F., Sachsenheimer, W., Schirmer, R. H. and Schulz, G. E. (1977)J. Mol. Biol.,144, 37.CrossRefGoogle Scholar
  58. Perutz,.. F. (1970)Nature (London),228, 726.CrossRefGoogle Scholar
  59. Perutz, M. F. (1979)Ann. Rev. Biochem., 48, 327.PubMedCrossRefGoogle Scholar
  60. Perutz, M. F. (1980)Proc. R. Soc. (London),B208, 135.Google Scholar
  61. Phillips, D. C. (1967)Proc. Natl. Acad. Sci. USA,57, 484.CrossRefGoogle Scholar
  62. Poole, P. L. and Finney, J. L. (1983)Biopolymers,22, 255.PubMedCrossRefGoogle Scholar
  63. Quiocho, F. A. and Lipscomb, W. N. (1971)Adv. Protein Chem.,25, 1.PubMedGoogle Scholar
  64. Remington, S., Weigand, G. and Huber, R. (1982)J. Mol. Biol.,158, 11.CrossRefGoogle Scholar
  65. Ribeiro, A. A., King, R. and Jardetzky, O. (1982) inConformation in Biology (eds R. Srinivasan and R. H. Sarma) (New York: Adenine Press), p. 39.Google Scholar
  66. Richardson, J. (1981)Adv. Protein Chem.,34, 167.PubMedCrossRefGoogle Scholar
  67. Rossmann, M. G., Liljas, A., Branden, C. I. and Banaszak, L. J. (1975) inThe Enzymes, ed. P. D. Boyer, 3rd edition, Vol. 11, p. 61.Google Scholar
  68. Rossmann, M. G., Moras, D. and Olsen, K. W. (1974)Nature (London),205, 194.CrossRefGoogle Scholar
  69. Sachsenheimer, W. and Schulz, G. E. (1977)J. Mol. Biol.,144, 23.CrossRefGoogle Scholar
  70. Salunke, D. M., Veerapandian, B. and Vijayan, M. (1984)Curr. Sci.,53, 231.Google Scholar
  71. Schulz, G. E., Elzinga, M, Marx, F. and Schirmer, R. H. (1974)Nature (London),250, 120.CrossRefGoogle Scholar
  72. Sigler, P. B., Blow, D. M., Matthews, B. W. and Henderson, R. (1968)J. Mol. Biol.,35, 143.PubMedCrossRefGoogle Scholar
  73. Steitz, T. A., Fletterick, R. J., Anderson, W. F. and Anderson, C. M. (1976)J. Mol. Biol.,104, 197.PubMedCrossRefGoogle Scholar
  74. Sternberg, M. J. E., Grace, D. E. P. and Phillips, D. C (1979)J. Mol. Biol.,130, 231.PubMedCrossRefGoogle Scholar
  75. Stubbs, G., Warren, S. and Holmes, K. (1977)Nature (London),267, 216.CrossRefGoogle Scholar
  76. Wagner, G. (1983)Q. Rev. Biophys.,16, 1.PubMedCrossRefGoogle Scholar
  77. Wiegand, G., Remington, S., Deisenhofer, J. and Huber, R. (1984)J. Mol. Biol.,174, 205.PubMedCrossRefGoogle Scholar
  78. Wetlaufer, D. B. (1973)Proc. Nat. Acad. Sci. (USA),70, 697.CrossRefGoogle Scholar
  79. White, J. L, Hackert, M. L, Buehner, M., Adams, M. J., Ford, G. C, Lentz, Jr. P. J., Smiley, I. E., Steindel, S. J. and Rossmann, M. G. (1976)J. Mol. Biol.,102, 759.PubMedCrossRefGoogle Scholar
  80. Woodward, C, Simon, I. and Tuchsen, E. (1982)Mol. Cell. Biochem.,48, 135.PubMedCrossRefGoogle Scholar
  81. Wright, C. S. (1977)J. Mol. Biol.,111, 439.PubMedCrossRefGoogle Scholar
  82. Wuthrich, K. and Wagner, G. (1979)Trends Biochem. Sci.,3, 227.CrossRefGoogle Scholar

Copyright information

© Indian Academy of Sciences 1984

Authors and Affiliations

  • M. Vijayan
    • 1
  • Dinakar M. Salunke
    • 1
  1. 1.Molecular Biophysics UnitIndian Institute of ScienceBangaloreIndia

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