Effects of turn stability on the kinetics of refolding of a hairpin in a β-sheet Article

Kuo, NNW, Huang, JJT, Miksovska, J et al. (2005). Effects of turn stability on the kinetics of refolding of a hairpin in a β-sheet . JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 127(48), 16945-16954. 10.1021/ja0543191

cited authors

  • Kuo, NNW; Huang, JJT; Miksovska, J; Chen, RPY; Larsen, RW; Chan, SI

authors

abstract

  • As part of our continuing study of the effects of the turn sequence on the conformational stability as well as the mechanism of folding of a β-sheet structure, we have undertaken a parallel investigation of the solution structure, conformational stability, and kinetics of refolding of the β-sheet VFIVDGOTYTEVD-PGOKILQ. The latter peptide is an analogue of the original Gellman β-sheet VFITSDPGKTYTEV DPGOKILQ, wherein the TSDPGK turn sequence in the first hairpin has been replaced by VDGO. Thermodynamics studies revealed comparable conformational stability of the two peptides. However, unlike the Gellman peptide, which showed extremely rapid refolding of the first hairpin, early kinetic events associated with the refolding of the corresponding hairpin in the VDGO mutant were found to be significantly slower. A detailed study of the conformation of the modified peptide suggested that hydrophobic interactions might be contributing to its stability. Accordingly, we surmise that the early kinetic events are sensitive to whether the formation of the hairpin is nucleated at the turn or by sequestering of the hydrophobic residues across the strand, before structural rearrangements to produce the nativelike topology. Nucleation of the hairpin at the turn is expected to be intrinsically rapid for a strong turn. However, if the process must involve collapse of hydrophobic side chains, the nucleation should be slower as solvent molecules must be displaced to sequester the hydrophobic residues. These findings reflect the contribution of different forces toward nucleation of hairpins in the mechanism of folding of β-sheets. © 2005 American Chemical Society.

publication date

  • December 7, 2005

published in

Digital Object Identifier (DOI)

start page

  • 16945

end page

  • 16954

volume

  • 127

issue

  • 48