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
Presta, L. G. & Rose, G. D. Science 240, 1632–1641 (1988).
Richardson, J. S. & Richardson, D. C. Science 240, 1648–1652 (1988).
Kim, P. S. & Baldwin, R. L. Nature 307, 329–334 (1984).
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).
Kellis, J. T. Jr, Nyberg, K., Sali, D. & Fersht, A. R. Nature 333, 784–786 (1988).
Sali, D., Bycroft, M. & Fersht, A. R. Nature 335, 741–743 (1988).
Kellis, J. T. Jr, Nyberg, K. & Fersht, A. R. Biochemistry 28, 4914–4922 (1989).
Matouschek, A., Kellis, J. T., Serrano, L. & Fersht, A. R. Nature 340, 122–126 (1989).
Mauguen, Y. et al. Nature 297, 162–164 (1982).
Hol, W. G. J. Prog. Biophys. molec. Biol. 45, 149–195 (1985).
Paddon, C. J. & Hartley, R. W. Gene 53, 11–19 (1987).
Strehlow, G. H. & Baldwin, L. R. Biochemistry 28, 2130–2133 (1989).
Matthews, B. W., Nicholson, H. & Becktel, W. J. Proc. natn. Acad. Sci. U.S.A. 84, 6663–6667 (1987).
Fersht, A. R. Trends Biochem. Sci. 12, 301–304 (1987).
Nicholson, H., Becktel, W. J. & Matthews, B. W. Nature 336, 651–656 (1988).
Studier, F. W., Rosenberg, A. H. & Dunn, J. J. Meth. Enzym. (in the press).
Serpesu, E. H., Shortle, D. & Mildvan, A. S. Biochemistry 25, 68–87 (1986).
Mossakowska, D. N., Nyberg, K. & Fersht, A. R. Biochemistry 28, 3843–3850 (1989).
Sayers, J. R. & Eckstein, F. In Genetic Engineering: Principles and Methods Vol. 10 (ed. Setlow, J. K.) 109 (Plenum, New York and London, 1988).
Carter, P. J., Winter, G., Wilkinson, A. J. & Fersht, A. R. Cell 38, 835–840 (1984).
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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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DOI: https://doi.org/10.1038/342296a0
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