title: The effect of charge-charge interactions on the kinetics of alpha-helix formation.
abstract: The formation of the monomeric alpha-helix represents one of the simplest scenarios in protein folding; however, our current understanding of the folding dynamics of the alpha-helix motif is mainly based on studies of alanine-rich model peptides. To examine the effect of peptide sequence on the folding kinetics of alpha-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 alpha-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.
authors: Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: Deguo
authors: D
authors: Du
authors: Michelle R
authors: MR
authors: Bunagan
authors: Feng
authors: F
authors: Gai
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D020916:Conotoxins; D036341:Intercellular Signaling Peptides and Proteins; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D020539:Sequence Analysis, Protein / Q000379:methods*; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D020916:Conotoxins; D036341:Intercellular Signaling Peptides and Proteins; D008978:Mollusk Venoms; D010455:Peptides; C063571:conantokin-T
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