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Measurement of the β-sheet-forming propensities of amino acids


SEVERAL model systems have been used to evaluate the α-helical propensities of different amino acids1–7. In contrast, experimental quantitation of β-sheet preferences has been addressed in only one model system, a zinc-finger peptide8. Here we measure the relative propensity for β-sheet formation of the twenty naturally occurring amino acids in a variant of the small, monomeric, β-sheet-rich, IgG-binding domain from protein G. Amino-acid substitutions were made at a guest site on the solvent-exposed surface of the β-sheet. Several criteria were used to establish that the mutations did not cause significant structural changes: binding to the Fc domain of IgG, calorimetric unfolding and NMR spectroscopy. Characterization of the thermal stabilities of these proteins leads to a thermodynamic scale for β-sheet propensities that spans a range of 2 kcal mol−1 for the naturally occurring amino acids, excluding proline. The magnitude of the differences suggests that β-sheet preferences can be important determinants of protein stability.

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  1. Scheraga, H. A. Pure appl. Chem. 50, 315–324 (1978)

    Article  CAS  Google Scholar 

  2. Padmanabhan, S., Marqusee, S., Ridgeway, T., Laue, T. M. & Baldwin, R. L. Nature 344, 268–270 (1990).

    Article  ADS  CAS  Google Scholar 

  3. O'Neil, K. T. & DeGrado, W. F. Science 250, 646–651 (1990).

    Article  ADS  CAS  Google Scholar 

  4. Lyu, P. C., Liff, M. I., Marky, L. A. & Kallenbach, N. R. Science 250, 669–673 (1990).

    Article  ADS  CAS  Google Scholar 

  5. Horovitz, A., Matthews, J. M. & Fersht, A. R. J. molec. Biol. 227, 560–568 (1992).

    Article  CAS  Google Scholar 

  6. Blaber, M., Zhang, X. & Matthews, B. W. Science 260, 1637–1640 (1993).

    Article  ADS  CAS  Google Scholar 

  7. Wojcik, J., Altman, K. H. & Scheraga, H. A. Biopolymers 30, 121–134 (1990).

    Article  CAS  Google Scholar 

  8. Kim, C. A. & Berg, J. M. Nature 362, 267–270 (1993).

    Article  ADS  CAS  Google Scholar 

  9. Alexander, P., Fahnestock, S., Lee, T., Orban, J. & Bryan, P. Biochemistry 31, 3597–3603 (1992).

    Article  CAS  Google Scholar 

  10. Gronenborn, A. M. et al. Science 253, 657–661 (1991).

    Article  ADS  CAS  Google Scholar 

  11. Chou, P. Y. & Fasman, G. D. Biochemistry 13, 211–222 (1973).

    Article  Google Scholar 

  12. Livingstone, J. R., Spolar, R. S. & Record, M. T. Jr Biochemistry 30, 4237–4244 (1991).

    Article  CAS  Google Scholar 

  13. Chakrabartty, A., Kortemme, T. S., Padmanabhan, S. & Baldwin, R. L. Biochemistry 32, 5560–5565 (1993).

    Article  CAS  Google Scholar 

  14. Vuilleumier, S., Sancho, J., Loewenthal, R. & Fersht, A. R. Biochemistry 32, 10303–10313 (1993).

    Article  CAS  Google Scholar 

  15. Fahnestock, S. R., Alexander, P., Filpula, D. & Nagle, J. in Bacterial Immunoglobin-Binding Proteins (ed. Boyle, M. D. P.) (Academic, San Diego, 1990).

    Google Scholar 

  16. Harlow, E. & Lane, D. Antibodies: A Laboratory Manual (Cold Spring Harbor Laboratory Press, New York, 1988).

    Google Scholar 

  17. Priestle, J. P. J. appl. Crystallogr. 21, 572–576 (1988).

    Article  Google Scholar 

  18. Oas, T. G. & Kim, P. S. Nature 336, 42–48 (1988).

    Article  ADS  CAS  Google Scholar 

  19. Fahnestock, S. R., Alexander, P., Nagle, J. & Filpula, D. J. Bact. 167, 870–880 (1986).

    Article  CAS  Google Scholar 

  20. Studier, F. W. & Moffat, B. A. J. molec. Biol. 189, 113–130 (1986).

    Article  CAS  Google Scholar 

  21. Doering, D. S. Functional and Structural Studies of a Small f-Actin Binding Domain (Massachusetts Institute of Technology Press, Cambridge, 1992).

    Google Scholar 

  22. Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory Press, New York, 1989).

    Google Scholar 

  23. Kunkel, T. A., Roberts, J. D. & Zakour, R. A. Meth. Enzym. 154, 367–382 (1987).

    Article  CAS  Google Scholar 

  24. Becktel, W. J. & Schellman, J. A. Biopolymers 26, 1859–1877 (1987).

    Article  CAS  Google Scholar 

  25. Edelhoch, H. Biochemistry 6, 1948–1954 (1967).

    Article  CAS  Google Scholar 

  26. Bodenhausen, G. & Ruben, D. J. Chem. Phys. Lett. 69, 185–189 (1980).

    Article  ADS  CAS  Google Scholar 

  27. DeMarco, A. J. magn. Reson. 26, 527–528 (1977).

    ADS  CAS  Google Scholar 

  28. Wüthrich, K. NMR of Proteins and Nucleic Acids (Wiley, New York, 1986).

    Book  Google Scholar 

  29. Mclntosh, L. P., Wand, A. J., Lowry, D. F., Redfield, A. G. & Dahlquist, F. W. Biochemistry 29, 6341–6362 (1990).

    Article  Google Scholar 

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Minor, D., Kim, P. Measurement of the β-sheet-forming propensities of amino acids. Nature 367, 660–663 (1994).

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