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Effect of alanine versus glycine in α-helices on protein stability

Nature volume 356, pages 453–455 (1992)Cite this article

Abstract

THE rational design of proteins requires knowledge of the helix-forming propensities (s-values) of the different amino acids. There is, however, considerable controversy about the relative values for alanine and glycine1–12We find from experiments on mutants of barnase that the relative effect of Ala versus Gly on helix stability depends crucially on the position in the helix (whether they are at the ends (caps) or are internal) and the context (the influence of their neighbours). Glycine is greatly preferred at the N and C caps. At internal positions, Ala stabilizes the helix relative to Gly by 0.4 to 2 kcal mol−1. The variation results from a combination of burial of hydrophobic surface on folding and interference with hydrogen bonding of the protein with solvent. There is a good empirical correlation between the relative stabilizing effects of Ala and Gly with the total change in solvent-accessible hydrophobic surface area of the folded protein on mutation of Gly to Ala. It is not valid to assign to each amino acid a unique s-value that is generally applicable to all positions in all helices in all proteins.

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References

  1. Sueki et al. Macromolecules 17, 148–155 (1984).

    Article  ADS  CAS  Google Scholar 

  2. Scheraga, H. A. Proc. natn. Acad. Sci U.S.A. 82, 5585–5587 (1985).

    Article  ADS  MathSciNet  CAS  Google Scholar 

  3. Altmann, K. H., Wojcik, J., Vasquez, M. & Scheraga, H. A. Biopolymers 30, 107–120 (1990).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  5. Merutka, G., Lipton, W., Shalongo, W., Park, S. H. & Stellwagen, E. Biochemistry 29, 7511–7515 (1990).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  7. Strehlow, K. G. & Baldwin, R. L. Biochemistry 28, 2130–2133 (1989).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  9. Marqusee, S., Robbins, V. H. & Baldwin, R. L. Proc. natn. Acad. Sci. U.S.A. 86, 5286–5290 (1989).

    Article  ADS  CAS  Google Scholar 

  10. Chakrabartty, A., Schellman, J. A. & Baldwin, R. L. Nature 351, 586–588 (1991).

    Article  ADS  CAS  Google Scholar 

  11. Kemp, D. S., Boyd, J. G. & Muendel, C. C. Nature 352, 451–454.

  12. Lesk, A. M. Nature 352, 379–380.

  13. Altman, K. H., Wojcik, J., Vasques, M. & Scheraga, H. A. Biopolymers 30, 107–120 (1990).

    Article  Google Scholar 

  14. Lifson, S. & Roig, A. J. J. chem. Phys. 34, 1963–1974 (1961).

    Article  ADS  CAS  Google Scholar 

  15. Serrano, L. & Fersht, A.R. Nature 342, 296–299 (1989).

    Article  ADS  CAS  Google Scholar 

  16. Sali, D., Bycroft, M. & Fersht, A. R. Nature 335, 563–567 (1988).

    Article  ADS  Google Scholar 

  17. Kellis, J. T. Jr, Nyberg, K., Sali, D. & Fersht, A. R. Nature 333, 784–786 (1988).

    Article  ADS  CAS  Google Scholar 

  18. Kellis, J. T. Jr, Nyberg, K. & Fersht, A. R. Biochemistry 28, 4914–4922 (1989).

    Article  CAS  Google Scholar 

  19. Horovitz, A., Serrano, L., Avron, B., Bycroft, M. & Fersht, A. R. J. molec. Biol. 216, 1031–1044 (1990).

    Article  CAS  Google Scholar 

  20. Horovitz, A., Serrano, L. & Fersht, A. R. J. molec. Biol. 219, 5–9 (1991).

    Article  CAS  Google Scholar 

  21. Serrano, L., Bycroft, M. & Fersht, A. R. J. molec. Biol. 218, 465–475 (1991).

    Article  CAS  Google Scholar 

  22. Presta, L. G. & Rose, G. D. Science 240, 2632–1641 (1988).

    Article  Google Scholar 

  23. Richardson, J. S. & Richardson, D. C. Science 240, 1648–1652 (1988).

    Article  ADS  CAS  Google Scholar 

  24. Hermann, R. B. J. phys. Chem. 76, 2754–2759 (1972).

    Article  CAS  Google Scholar 

  25. Harris, M. J., Higuchi, T. & Rytting, J. J. phys. Chem. 77, 2694–2702 (1972).

    Article  Google Scholar 

  26. Reynolds, J. A., Gilbert, D. B. & Tanford, C. Proc. natn. Acad. Sci. U.S.A. 71, 2925–2927 (1974).

    Article  ADS  CAS  Google Scholar 

  27. Chothia, C. Nature 248, 338–339 (1974).

    Article  ADS  CAS  Google Scholar 

  28. Kellis, J. T. Jr, Nyberg, K. & Fersht, A. R. Biochemistry 28, 4914–4922 (1989).

    Article  CAS  Google Scholar 

  29. Serrano, L., Kellis, J. T., Cann, P., Matouschek, A. & Fersht, A. R. J. molec. Biol. (in the press).

  30. Sharp, K. A., Nicholls, A., Friedman, R. & Honig, B. Biochemistry 30, 9686–9697 (1991).

    Article  CAS  Google Scholar 

  31. Matthews, B. W., Nicholson, H. & Becktel, W. J. Proc. natn. Acad. Sci. U.S.A. 84, 6663–6667 (1987).

    Article  ADS  CAS  Google Scholar 

  32. Richards, F. M. & Richmond, T. Ciba Fdn Symp. 60, 23–37 (1978).

    CAS  Google Scholar 

  33. Shrake, A. & Rupley, J. A. J. molec. Biol. 79, 351–371 (1973).

    Article  CAS  Google Scholar 

  34. Miller, S., Janin, J., Lesk, A. M. & Chothia, C. J. molec. Biol. 196, 641–656 (1987).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. MRC Unit for Protein Function and Design, Cambridge IRC for Protein Engineering, MRC Centre, Hills Road, Cambridge, CB2 2QH, UK

    Luis Serrano, Jose-Luis Neira, Javier Sancho & Alan R. Fersht

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  1. Luis Serrano
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  2. Jose-Luis Neira
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  3. Javier Sancho
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  4. Alan R. Fersht
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Serrano, L., Neira, JL., Sancho, J. et al. Effect of alanine versus glycine in α-helices on protein stability. Nature 356, 453–455 (1992). https://doi.org/10.1038/356453a0

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