Understanding the key factors that control the rate of β-hairpin folding

被引:191
作者
Du, DG [1 ]
Zhu, YJ [1 ]
Huang, CY [1 ]
Gai, F [1 ]
机构
[1] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA
关键词
D O I
10.1073/pnas.0405904101
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Both turn sequence and interstrand hydrophobic side-chain-side-chain interaction have been suggested to be important determinants of beta-hairpin stability. However, their roles in controlling the folding dynamics of beta-hairpins have not been clearly determined. Herein, we investigated the structural stability and folding kinetics of a series of tryptophan zippers by static IR and CD spectroscopies and the IR temperature jump method. Our results support a beta-hairpin folding mechanism wherein the rate-limiting event corresponds to the formation of the turn. We find that the logarithm of the folding rate depends linearly on the entropic change associated with the turn formation, where faster folding correlates with lower entropic cost. Moreover, a stronger turn-promoting sequence increases the stability of a beta-hairpin primarily by increasing its folding rate, whereas a stronger hydrophobic cluster increases the stability of a beta-hairpin primarily by decreasing its unfolding rate.
引用
收藏
页码:15915 / 15920
页数:6
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