Structural studies of RNA-protein complexes: A hybrid approach involving hydrodynamics, scattering, and computational methods
Structural studies of RNA-protein complexes: A hybrid approach involving hydrodynamics, scattering, and computational methods
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DOI：
10.1016/j.ymeth.2016.12.002
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发表时间：
2017-04-15
期刊：
影响因子：
4.8
通讯作者：
Bujnicki, Janusz M.
中科院分区：
文献类型：
--
作者：
Patel, Trushar R.;Chojnowski, Grzegorz;Bujnicki, Janusz M.
核糖核酸（RNA）所扮演的各种功能细胞的角色，强调了需要开发快速和准确的方法来阐明RNA的结构和功能之间的关系。结构生物学工具，如X射线晶体学和核磁共振是非常有用的方法，以获得原子级分辨率的大分子模型。然而，这两种方法都具有样品、时间和技术限制，这阻止了它们应用于许多感兴趣的大分子。高分辨率结构技术的一种新兴替代方案是采用混合方法，该方法将来自实验流体动力学（例如分析超离心）和溶液散射测量（例如，溶液X射线或中子散射），并通过计算建模来获得原子级模型。虽然很有前途，但散射方法依赖于无聚集、单分散的制剂，因此仔细开发质量控制管道是进行无偏和可靠结构测定的基础。这篇综述文章介绍了流体动力学技术，是非常有价值的均匀性研究，散射技术有助于研究低分辨率的形状，和计算建模的策略，以获得高分辨率的RNA，蛋白质和RNA-蛋白质复合物的三维结构模型。(C)2016作者（S）爱思唯尔公司出版
The diverse functional cellular roles played by ribonucleic acids (RNA) have emphasized the need to develop rapid and accurate methodologies to elucidate the relationship between the structure and function of RNA. Structural biology tools such as X-ray crystallography and Nuclear Magnetic Resonance are highly useful methods to obtain atomic-level resolution models of macromolecules. However, both methods have sample, time, and technical limitations that prevent their application to a number of macromolecules of interest. An emerging alternative to high-resolution structural techniques is to employ a hybrid approach that combines low-resolution shape information about macromolecules and their complexes from experimental hydrodynamic (e.g. analytical ultracentrifugation) and solution scattering measurements (e.g., solution X-ray or neutron scattering), with computational modeling to obtain atomic level models. While promising, scattering methods rely on aggregation-free, monodispersed preparations and therefore the careful development of a quality control pipeline is fundamental to an unbiased and reliable structural determination. This review article describes hydrodynamic techniques that are highly valuable for homogeneity studies, scattering techniques useful to study the low-resolution shape, and strategies for computational modeling to obtain high-resolution 3D structural models of RNAs, proteins, and RNA-protein complexes. (C) 2016 The Author(s). Published by Elsevier Inc.