Effects of Turn Stability on the Kinetics of Refolding of a Hairpin in a -sheet
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- 作者：Nicole N.-W. Kuo ; Joseph J.-T. Huang ; Jaroslava Miksovska ; Rita P.-Y. Chen ; Randy W. Larsen ; and Sunney I. Chan
- 刊名：Journal of the American Chemical Society
- 出版年：2005
- 出版时间：December 7, 2005
- 年：2005
- 卷：127
- 期：48
- 页码：16945 - 16954
- 全文大小：632K
- 年卷期：v.127,no.48(December 7, 2005)
- ISSN：1520-5126
文摘
As part of our continuing study of the effects of the turn sequence on the conformational stabilityas well as the mechanism of folding of a 
-sheet structure, we have undertaken a parallel investigation ofthe solution structure, conformational stability, and kinetics of refolding of the -sheet VFIVDGOTYTEVDPGOKILQ. The latter peptide is an analogue of the original Gellman -sheet VFITSDPGKTYTEVDPGOKILQ,wherein the TSDPGK turn sequence in the first hairpin has been replaced by VDGO. Thermodynamicsstudies revealed comparable conformational stability of the two peptides. However, unlike the Gellmanpeptide, which showed extremely rapid refolding of the first hairpin, early kinetic events associated withthe refolding of the corresponding hairpin in the VDGO mutant were found to be significantly slower. Adetailed study of the conformation of the modified peptide suggested that hydrophobic interactions mightbe contributing to its stability. Accordingly, we surmise that the early kinetic events are sensitive to whetherthe formation of the hairpin is nucleated at the turn or by sequestering of the hydrophobic residues acrossthe strand, before structural rearrangements to produce the nativelike topology. Nucleation of the hairpinat the turn is expected to be intrinsically rapid for a strong turn. However, if the process must involvecollapse of hydrophobic side chains, the nucleation should be slower as solvent molecules must be displacedto sequester the hydrophobic residues. These findings reflect the contribution of different forces towardnucleation of hairpins in the mechanism of folding of -sheets.
-sheet structure, we have undertaken a parallel investigation ofthe solution structure, conformational stability, and kinetics of refolding of the -sheet VFIVDGOTYTEVDPGOKILQ. The latter peptide is an analogue of the original Gellman -sheet VFITSDPGKTYTEVDPGOKILQ,wherein the TSDPGK turn sequence in the first hairpin has been replaced by VDGO. Thermodynamicsstudies revealed comparable conformational stability of the two peptides. However, unlike the Gellmanpeptide, which showed extremely rapid refolding of the first hairpin, early kinetic events associated withthe refolding of the corresponding hairpin in the VDGO mutant were found to be significantly slower. Adetailed study of the conformation of the modified peptide suggested that hydrophobic interactions mightbe contributing to its stability. Accordingly, we surmise that the early kinetic events are sensitive to whetherthe formation of the hairpin is nucleated at the turn or by sequestering of the hydrophobic residues acrossthe strand, before structural rearrangements to produce the nativelike topology. Nucleation of the hairpinat the turn is expected to be intrinsically rapid for a strong turn. However, if the process must involvecollapse of hydrophobic side chains, the nucleation should be slower as solvent molecules must be displacedto sequester the hydrophobic residues. These findings reflect the contribution of different forces towardnucleation of hairpins in the mechanism of folding of -sheets.