How random are intrinsically disordered proteins? A small angle scattering perspective.
How random are intrinsically disordered proteins? A small angle scattering perspective.
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DOI：
10.2174/138920312799277901
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发表时间：
2012-02
影响因子：
2.8
通讯作者：
Durand D
中科院分区：
文献类型：
--
作者：
Receveur-Brechot V;Durand D
虽然现在已经认识到内在无序蛋白（IDPs）在细胞周期中的关键作用，但在结构水平上破译其分子作用模式仍然具有很高的挑战性，需要多种生物物理方法的结合。其中，小角度x射线散射（SAXS）在过去十年中取得了极大的成功，并已成为解决有关境内流离失所者活动的许多基本问题的必不可少的技术。在介绍了一些特定于IDPs的实验问题和与最新技术发展相关的问题之后，本文介绍了聚合物物理理论对评估完全无序蛋白质柔韧性的兴趣。不同的策略，以获得三维模型的国内流离失所者，自由的解决方案和相关的复杂，然后进行了审查。事实上，最近的计算进步使得从散射曲线中提取最大信息成为可能，特别强调高度灵活的系统，如多结构域蛋白质和IDPs。此外，集成的计算方法现在可以通过考虑越来越多的各种互补实验的约束，生成构象集合来转化IDPs独特的柔性特性。特别是，SAXS与高分辨率技术的结合，如x射线晶体学和核磁共振，使我们能够提供可靠的模型，并在多个结构尺度上获得关于蛋白质的独特结构见解。最新的中子散射实验也有望在涉及更复杂系统的大分子构象变化的研究中取得新的进展。
While the crucial role of intrinsically disordered proteins (IDPs) in the cell cycle is now recognized, deciphering their molecular mode of action at the structural level still remains highly challenging and requires a combination of many biophysical approaches. Among them, small angle X-ray scattering (SAXS) has been extremely successful in the last decade and has become an indispensable technique for addressing many of the fundamental questions regarding the activities of IDPs. After introducing some experimental issues specific to IDPs and in relation to the latest technical developments, this article presents the interest of the theory of polymer physics to evaluate the flexibility of fully disordered proteins. The different strategies to obtain 3-dimensional models of IDPs, free in solution and associated in a complex, are then reviewed. Indeed, recent computational advances have made it possible to readily extract maximum information from the scattering curve with a special emphasis on highly flexible systems, such as multidomain proteins and IDPs. Furthermore, integrated computational approaches now enable the generation of ensembles of conformers to translate the unique flexible characteristics of IDPs by taking into consideration the constraints of more and more various complementary experiment. In particular, a combination of SAXS with high-resolution techniques, such as x-ray crystallography and NMR, allows us to provide reliable models and to gain unique structural insights about the protein over multiple structural scales. The latest neutron scattering experiments also promise new advances in the study of the conformational changes of macromolecules involving more complex systems.