ALPHA-HELIX CAPPING IN SYNTHETIC MODEL PEPTIDES BY RECIPROCAL SIDE-CHAIN MAIN-CHAIN INTERACTIONS - EVIDENCE FOR AN N-TERMINAL CAPPING BOX

A significant fraction of the amino acids in proteins are alpha helica l in conformation. Alpha helices in globular proteins are short, with an average length of about twelve residues, so that residues at the en ds of helices make up an important fraction of all helical residues. I n the middle of a helix, H-bonds connect the NH and CO groups of each residue to partners four residues along the chain. At the ends of a he lix, the H-bond potential of the main chain remains unfulfilled, and h elix capping interactions involving bonds from polar side chains to th e NH or CO of the backbone have been proposed and detected. In a study of synthetic helical peptides, we have found that the sequence Ser-Gl u-Asp-Glu stabilizes the alpha helix in a series of helical peptides w ith consensus sequences. Following the report by Harper and Rose, whic h indentifies SerXAaXaaGlu as a member of a class of common motifs at the N termini of alpha helices in proteins that they refer to as ''cap ping boxes,'' we have reexamined the side chain-main chain interaction s in a varient sequence using H-1 NMR, and find that the postulated re ciprocal side chain-backbone bonding between the first Ser and last Gl u side chains and their peptide NH partners can be resolved. Deletion of two residues N terminal to the Ser-Glu-Asp-Glu sequence in these pe ptides has no effect on the initiation of helical structure, as define d by two-dimensional (2D) NMR experiments on this variant. Thus the ca pping box sequence Ser-Glu-Asp-Glu inhibits N terminal fraying of the N terminus of alpha helix in these peptides, and shows the side chain- main chain interactions proposed by Harper and Rose. It thus acts as a helix initiating signal. Since normal alpha helix cannot propagate be yond the N terminus of this structure, the box acts as a termination s ignal in this direction as well. (C) 1994 Wiley-Liss, Inc.