Capping and α-helix stability

Abstract

THE first and last four residues of α-helices differ from the rest by not being able to make the intrehelical hydrogen bonds between the backbone >C=O groups of one turn and the >NH groups of the next1. Physico-chemical arguments1 and statistical analysis2 suggest that there is a preference for certain residues at the C and N termini (the C- and N-caps)2 that can fulfil the hydrogen bonding requirements. We have tested this hypothesis by constructing a series of mutations in the two N-caps of barnase (Bacillus amyloliquefaciens ribonuclease, positions Thr 6 and Thr 26) and determining the change in their stability. The N-cap is found to stabilize the protein by up to ~2.5 kcal mol−1. The presence of a negative charge of the N-cap adds some 1.6 kcal mol−1 of stabilization energy because of the interaction with the macroscopic electrostatic dipole of the helix.

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References

  1. 1

    Presta, L. G. & Rose, G. D. Science 240, 1632–1641 (1988).

    ADS  CAS  Article  Google Scholar 

  2. 2

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

    ADS  CAS  Article  Google Scholar 

  3. 3

    Kim, P. S. & Baldwin, R. L. Nature 307, 329–334 (1984).

    ADS  CAS  Article  Google Scholar 

  4. 4

    Shoemaker, K., Kim, P. S., York, E. J., Stewart, J. M. & Baldwin, R. L. Proc. natn. Acad. Sci. U.S.A. 82, 2349–2353 (1985); Nature 326, 563–567 (1987).

    ADS  CAS  Article  Google Scholar 

  5. 5

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

    ADS  CAS  Article  Google Scholar 

  6. 6

    Sali, D., Bycroft, M. & Fersht, A. R. Nature 335, 741–743 (1988).

    ADS  Google Scholar 

  7. 7

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

    CAS  Article  Google Scholar 

  8. 8

    Matouschek, A., Kellis, J. T., Serrano, L. & Fersht, A. R. Nature 340, 122–126 (1989).

    ADS  CAS  Article  Google Scholar 

  9. 9

    Mauguen, Y. et al. Nature 297, 162–164 (1982).

    ADS  CAS  Article  Google Scholar 

  10. 10

    Hol, W. G. J. Prog. Biophys. molec. Biol. 45, 149–195 (1985).

    CAS  Article  Google Scholar 

  11. 11

    Paddon, C. J. & Hartley, R. W. Gene 53, 11–19 (1987).

    CAS  Article  Google Scholar 

  12. 12

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

    CAS  Article  Google Scholar 

  13. 13

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

    ADS  CAS  Article  Google Scholar 

  14. 14

    Fersht, A. R. Trends Biochem. Sci. 12, 301–304 (1987).

    CAS  Article  Google Scholar 

  15. 15

    Nicholson, H., Becktel, W. J. & Matthews, B. W. Nature 336, 651–656 (1988).

    ADS  CAS  Article  Google Scholar 

  16. 16

    Studier, F. W., Rosenberg, A. H. & Dunn, J. J. Meth. Enzym. (in the press).

  17. 17

    Serpesu, E. H., Shortle, D. & Mildvan, A. S. Biochemistry 25, 68–87 (1986).

    Article  Google Scholar 

  18. 18

    Mossakowska, D. N., Nyberg, K. & Fersht, A. R. Biochemistry 28, 3843–3850 (1989).

    CAS  Article  Google Scholar 

  19. 19

    Sayers, J. R. & Eckstein, F. In Genetic Engineering: Principles and Methods Vol. 10 (ed. Setlow, J. K.) 109 (Plenum, New York and London, 1988).

    Google Scholar 

  20. 20

    Carter, P. J., Winter, G., Wilkinson, A. J. & Fersht, A. R. Cell 38, 835–840 (1984).

    CAS  Article  Google Scholar 

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Serrano, L., Fersht, A. Capping and α-helix stability. Nature 342, 296–299 (1989). https://doi.org/10.1038/342296a0

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