arXiv 1002.24552010-02-12q-bio.BM

单残基微扰对蛋白质构象变化的调控

Manipulation of conformational change in proteins by single residue perturbations

C Atilgan, Z N Gerek, S B Ozkan, A R Atilgan

DOI：: 10.1016/j.bpj.2010.05.020

摘要：

使用扰动响应扫描（PRS）技术，我们研究了一组23个蛋白质，显示各种构象运动后配体结合（如剪切，铰链，变构）。在大多数情况下，PRS确定可以被操纵以实现所得构象变化的残基。PRS表明，对于某些蛋白质，结合诱导的构象变化可以通过扰动分散在整个蛋白质中的残基来实现，而在其他蛋白质中，仅限于高度特异性区域的特定残基的扰动是必要的。实验和计算的原子位移之间的相关性总是更好或等效于从弹性网络模型的模态分析中获得的那些。此外，最好的相关性获得后一种方法并不总是出现在最集体的模式。我们表明，成功的模态分析取决于缺乏冗余的路径，存在于蛋白质。因此，PRS表明，几个相关的模式可以同时诱导通过扰动蛋白质上的一个单一的选择残基。我们还详细说明了应用PRS的GroEL和ADK结构的生物相关性，在那里我们表明，其扰动导致精确的构象变化的残基通常对应于那些实验确定的功能重要。

英文摘要：

Using the perturbation-response scanning (PRS) technique, we study a set of 23 proteins that display a variety of conformational motions upon ligand binding (e.g. shear, hinge, allosteric). In most cases, PRS determines residues that may be manipulated to achieve the resulting conformational change. PRS reveals that for some proteins, binding induced conformational change may be achieved through the perturbation of residues scattered throughout the protein, whereas in others, perturbation of specific residues confined to a highly specific region are necessary. Correlations between the experimental and calculated atomic displacements are always better or equivalent to those obtained from a modal analysis of elastic network models. Furthermore, best correlations obtained by the latter approach do not always appear in the most collective modes. We show that success of the modal analysis depends on the lack of redundant paths that exist in the protein. PRS thus demonstrates that several relevant modes may simultaneously be induced by perturbing a single select residue on the protein. We also illustrate the biological relevance of applying PRS on the GroEL and ADK structures in detail, where we show that the residues whose perturbation lead to the precise conformational changes usually correspond to those experimentally determined to be functionally important.

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英文摘要：

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