Helix stop and start signals in peptides and proteins. The capping box does not necessarily prevent helix elongation.

Recently, several papers have addressed the existence of helix stop signals at the beginning of alpha-helices. It has been indicated that the existence of a reciprocal backbone-side-chain hydrogen-bond interaction, designated the capping box, could be one of these signals. The fingerprint sequence of this capping box is Ser/Thr-X-X-Glu/Gln. In the fifth alpha-helix of the chemotactic alpha/beta parallel protein CheY there is such a sequence in the middle of the helix. In a peptide corresponding to this alpha-helix the capping box is bypassed, as deduced from NMR analysis. However, making the peptide shorter so that the capping box fingerprint is closer to the beginning of the peptide results in the formation of the capping box. These results indicate that, although the capping box could play a role in stabilizing and nucleating helical peptides in solution, it is not necessarily a stop signal and can be bypassed when favourable interactions exist between the surrounding residues.