Santiveri Clara M, Santoro Jorge, Rico Manuel, Jiménez M Angeles
Instituto de Química-Física Rocasolano, Consejo Superior de Investigaciones Científicas, Serrano 119, 28006-Madrid, Spain.
J Am Chem Soc. 2002 Dec 18;124(50):14903-9. doi: 10.1021/ja0278537.
The temperature dependence of the (1)H chemical shifts of six designed peptides previously shown to adopt beta-hairpin structures in aqueous solution has been analyzed in terms of two-state (beta-hairpin left arrow over right arrow coil) equilibrium. The stability of the beta-hairpins formed by these peptides, as derived from their T(m) (midpoint transition temperature) values, parallels in general their ability to adopt those structures as deduced from independent NMR parameters: NOEs, Deltadelta(C)(alpha)(H), Deltadelta(C)(alpha), and Deltadelta(C)(beta) values. The observed T(m) values are dependent on the particular position within the beta-hairpin that is probed, indicating that their folding to a beta-hairpin conformation deviates from a "true" two-state transition. To obtain individual T(m) values for each hairpin region in each peptide, a simplified model of a successive uncoupled two-state equilibrium covering the entire process has been applied. The distribution of T(m) values obtained for the different beta-hairpin regions (turn, strands, backbone, side chains) in the six analyzed peptides reveals a similar pattern. A model for beta-hairpin folding is proposed on the basis of this pattern and the reasonable assumption that regions showing higher T(m) values are the last ones to unfold and, presumably, the first to form. With this assumption, the analysis suggests that turn formation is the first event in beta-hairpin folding. This is consistent with previous results on the essential role of the turn sequence in beta-hairpin folding.
先前已证明在水溶液中呈现β-发夹结构的六种设计肽的（1）H化学位移的温度依赖性，已根据两态（β-发夹⇄卷曲）平衡进行了分析。由这些肽形成的β-发夹的稳定性，从其T（m）（中点转变温度）值推导得出，总体上与从独立的NMR参数（NOEs、Δδ（C）α（H）、Δδ（C）α和Δδ（C）β值）推断出的它们采用那些结构的能力平行。观察到的T（m）值取决于在β-发夹中被探测的特定位置，这表明它们折叠成β-发夹构象偏离了“真正的”两态转变。为了获得每种肽中每个发夹区域的个体T（m）值，已应用了一个涵盖整个过程的连续解耦两态平衡的简化模型。在六种分析肽中，针对不同β-发夹区域（转角、链、主链、侧链）获得的T（m）值分布揭示了一种相似的模式。基于这种模式以及合理的假设，即显示较高T（m）值的区域是最后展开且大概是最先形成的区域，提出了一种β-发夹折叠模型。基于这一假设，分析表明转角形成是β-发夹折叠中的首个事件。这与先前关于转角序列在β-发夹折叠中的重要作用的结果一致。
