Toward a molecular understanding of the anisotropic response of proteins to external forces: Insights from elastic network models
Toward a molecular understanding of the anisotropic response of proteins to external forces: Insights from elastic network models
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DOI：
10.1529/biophysj.107.120733
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发表时间：
2008-05-01
影响因子：
3.4
通讯作者：
Bahar, Ivet
中科院分区：
文献类型：
--
作者：
Eyal, Eran;Bahar, Ivet
随着单分子操作技术的最新进展，现在可以测量蛋白质对施加在特定位置的外部拉力的机械阻力。值得注意的是，这些最近的研究表明，启动展开所需的拉力/拉伸力根据施加力的位置而变化很大，从而解开蛋白质对单轴张力的残留/位置特异性响应。在这里，我们表明，粗粒度的弹性网络模型的基础上的拓扑结构的interresidue接触在本地状态可以令人满意地解释这种拉伸力施加在不同的残基对的相对大小。尽管它们很简单，但这些模型大概捕捉到了一个支配观察到的行为的基本属性：结构固有地倾向于相对较低频率的运动模式所能适应的变形需要较弱的力，反之亦然。因此，蛋白质对外部应力的机械响应与折叠状态中固有的各向异性波动动力学相关。对整体折叠的依赖性意味着具有共同结构特征的进化相关蛋白质往往具有相似的机械性质。然而，该理论不能解释在许多结构相似但顺序遥远的结构域中观察到的差异，例如纤连蛋白结构域。
With recent advances in single-molecule manipulation techniques, it is now possible to measure the mechanical resistance of proteins to external pulling forces applied at specific positions. Remarkably, such recent studies demonstrated that the pulling/stretching forces required to initiate unfolding vary considerably depending on the location of the application of the forces, unraveling residue/position-specific response of proteins to uniaxial tension. Here we show that coarse-grained elastic network models based on the topology of interresidue contacts in the native state can satisfactory explain the relative sizes of such stretching forces exerted on different residue pairs. Despite their simplicity, such models presumably capture a fundamental property that dominates the observed behavior: deformations that can be accommodated by the relatively lower frequency modes of motions intrinsically favored by the structure require weaker forces and vice versa. The mechanical response of proteins to external stress is therefore shown to correlate with the anisotropic fluctuation dynamics intrinsically accessible in the folded state. The dependence on the overall fold implies that evolutionarily related proteins sharing common structural features tend to possess similar mechanical properties. However, the theory cannot explain the differences observed in a number of structurally similar but sequentially distant domains, such as the fibronectin domains.