Application of NMR to studies of intrinsically disordered proteins
Application of NMR to studies of intrinsically disordered proteins
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DOI：
10.1016/j.abb.2017.05.008
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发表时间：
2017-08-15
影响因子：
3.9
通讯作者：
Showalter, Scott A.
中科院分区：
文献类型：
--
作者：
Gibbs, Eric B.;Cook, Erik C.;Showalter, Scott A.
特别是在真核生物蛋白质中，蛋白质区域的存在及其在信号和基因调控方面的明显功能优势，为高分辨率的结构和机制研究创造了迫切的条件。核磁共振光谱学不仅在增强我们对固有无序状态的理解方面发挥了核心作用，而且还在增强这种状态对生物功能的贡献方面发挥了核心作用。虽然与蛋白质聚集相关的病理功能已经确立，但最近已经清楚的是，无序区域也介导功能优势的组装形成高阶结构，促进无膜亚细胞隔室甚至水凝胶的形成。在无序区域进入的功能组装状态的范围内，翻译后修饰和调节性大分子相互作用，这也可以通过核磁共振光谱进行研究，具有显著的特点。在这里，我们将探索核磁共振在许多方面促进了我们对蛋白质无序区域所占据的物理化学相空间的理解，并为核磁共振在这一新兴和令人兴奋的领域中的未来角色提供了展望。(C)2017 Elsevier Inc.保留所有权利。
The prevalence of intrinsically disordered protein regions, particularly in eukaryotic proteins, and their clear functional advantages for signaling and gene regulation have created an imperative for high resolution structural and mechanistic studies. NMR spectroscopy has played a central role in enhancing not only our understanding of the intrinsically disordered native state, but also how that state contributes to biological function. While pathological functions associated with protein aggregation are well established, it has recently become clear that disordered regions also mediate functionally advantageous assembly into high-order structures that promote the formation of membrane-less sub-cellular compartments and even hydrogels. Across the range of functional assembly states accessed by disordered regions, post-translational modifications and regulatory macromolecular interactions, which can also be investigated by NMR spectroscopy, feature prominently. Here we will explore the many ways in which NMR has advanced our understanding of the physical-chemical phase space occupied by disordered protein regions and provide prospectus for the future role of NMR in this emerging and exciting field. (C) 2017 Elsevier Inc. All rights reserved.