Positional effects of phosphoserine on β-hairpin stability.

A disruptive interaction of phosphoserine with tryptophan in peptides that autonomously fold into a β-hairpin structure in aqueous solution was explored in a positional context within the hairpin structure. All the peptides presented here have a serine or phosphoserine directly cross strand from a tryptophan residue in the β-hairpin structure. It was observed that positioning of phosphoserine-tryptophan had a less destabilizing effect if the phosphoserine was on the C-terminus as opposed to the N-terminus. Greater destabilization was observed when the phosphoserine was positioned closer to the nucleating turn sequence rather than the termini of the hairpin. Multiple phosphorylations in a hairpin designed with two cross-strand serine-tryptophan pairs resulted in a greater decrease in hairpin formation with additional incorporations of phosphoserine. The work presented here gives further insight to destabilizing phosphoserine-tryptophan interaction within the β-hairpin model system.