Capping and α-helix stability


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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Serrano, L., Fersht, A. Capping and α-helix stability. Nature 342, 296–299 (1989).

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