Folding dynamics and mechanism of beta-hairpin formation
Folding dynamics and mechanism of beta-hairpin formation
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DOI：
10.1038/36626
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发表时间：
1997-11-13
期刊：
影响因子：
64.8
通讯作者：
Eaton, WA
中科院分区：
文献类型：
--
作者：
Munoz, V;Thompson, PA;Eaton, WA
蛋白质链卷曲成α螺旋和β折叠结构。了解这些基本结构元素的形成时间尺度和机制对于理解蛋白质如何折叠至关重要（1）。在过去的40年里，α-螺旋的形成已经在合成和天然肽（2-5）中被广泛研究，包括纳秒动力学研究（6，7）。相反，β结构的形成机制还没有实验研究。最小的β-结构元件是β-发夹，它也是反平行β-折叠的基本组成部分。在这里，我们使用纳秒激光温度跳跃装置来研究折叠由16个氨基酸残基组成的β-发夹的动力学。在室温下，发夹的折叠在6 μ s内发生，这比α-螺旋形成的速率慢约30倍（6，7）。我们已经开发了一个简单的统计力学模型，为这一结果提供了结构上的解释，我们的分析还表明，β-发夹的折叠捕获了蛋白质折叠的大部分基本物理学;包括氢键和疏水相互作用的稳定性，双态行为，以及漏斗状，部分崎岖的能量景观。
Protein chains coil into alpha-helices and beta-sheet structures. Knowing the timescales and mechanism of formation of these basic structural elements is essential for understanding how proteins fold(1). For the past 40 years, alpha-helix formation has been extensively investigated in synthetic and natural peptides(2-5), including by nanosecond kinetic studies(6,7). In contrast, the mechanism of formation of beta structures has not been studied experimentally. The minimal beta-structure element is the beta-hairpin, which is also the basic component of antiparallel beta-sheets. Here we use a nanosecond laser temperature-jump apparatus to study the kinetics of folding a beta-hairpin consisting of 16 amino-acid residues. Folding of the hairpin occurs in 6 mu s at room temperature, which is about 30 times slower than the rate of alpha-helix formation(6,7). We have developed a simple statistical mechanical model that provides a structural explanation for this result, Our analysis also shows that folding of a beta-hairpin captures much of the basic physics of protein folding; including stabilization by hydrogen bonding and hydrophobic interactions, two-state behaviour, and a funnel-like, partially rugged energy landscape.