The Effect of Charge-Charge Interactions on the Kinetics of α-Helix Formation

The formation of the monomeric α-helix represents one of the simplest scenarios in protein folding; however, our current understanding of the folding dynamics of the α-helix motif is mainly based on studies of alanine-rich model peptides. To examine the effect of peptide sequence on the folding kinetics of α-helices, we studied the relaxation kinetics of a 21-residue helical peptide, Conantokin-T (Con-T), using time-resolved infrared spectroscopy in conjunction with a laser-induced temperature jump technique. Con-T is a neuroactive peptide containing a large number of charged residues that is found in the venom of the piscivorous cone snail Conus tulipa. The temperature-jump relaxation kinetics of Con-T is distinctly slower than that of previously studied alanine-based peptides, suggesting that the folding time of α-helices is sequence-dependent. Furthermore, it appears that the slower folding of Con-T can be attributed to the fact that its helical conformation is stabilized by charge-charge interactions or salt bridges. Although this finding contradicts an earlier molecular dynamics simulation, it also has implications for existing models of protein folding.