Institute of Structural Biology, Helmholtz Zentrum München, Neuherberg, Germany; Bavarian NMR Center and Center for Integrated Protein Science Munich at Department Chemie, Technical University of Munich, Garching, Germany.
University Grenoble Alpes, CEA, CNRS, IBS, Grenoble, France.
J Mol Biol. 2020 Apr 17;432(9):2890-2912. doi: 10.1016/j.jmb.2020.03.014. Epub 2020 Mar 19.
The study of complex and dynamic biomolecular assemblies is a key challenge in structural biology and requires the use of multiple methodologies providing complementary spatial and temporal information. NMR spectroscopy is a powerful technique that allows high-resolution structure determination of biomolecules as well as investigating their dynamic properties in solution. However, for high-molecular-weight systems, such as biomolecular complexes or multi-domain proteins, it is often only possible to obtain sparse NMR data, posing significant challenges to structure determination. Combining NMR data with information obtained from other solution techniques is therefore an attractive approach. The combination of NMR with small-angle X-ray and/or neutron scattering has been shown to be particularly fruitful. These scattering approaches provide low-resolution information of biomolecules in solution and reflect ensemble-averaged contributions of dynamic conformations for scattering molecules up to megadalton molecular weight. Here, we review recent developments in the combination of nuclear magnetic resonance spectroscopy (NMR) and small-angle scattering (SAS) experiments. We briefly outline the different types of information that are provided by these techniques. We then discuss computational methods that have been developed to integrate NMR and SAS data, particularly considering the presence of dynamic structural ensembles and flexibility of the investigated biomolecules. Finally, recent examples of the successful combination of NMR and SAS are presented to illustrate the utility of their combination.
研究复杂和动态的生物分子组装体是结构生物学的一个关键挑战，需要使用多种方法学提供互补的空间和时间信息。NMR 光谱学是一种强大的技术，它允许对生物分子进行高分辨率结构测定，并研究它们在溶液中的动态特性。然而，对于高分子量系统，如生物分子复合物或多结构域蛋白质，通常只能获得稀疏的 NMR 数据，这对结构测定提出了重大挑战。因此，将 NMR 数据与从其他溶液技术获得的信息结合起来是一种有吸引力的方法。已经证明，将 NMR 与小角 X 射线和/或中子散射相结合特别有成效。这些散射方法提供了溶液中生物分子的低分辨率信息，并反映了散射分子的动态构象的平均集合贡献，可达兆道尔顿分子量。在这里，我们综述了核磁共振波谱学（NMR）和小角散射（SAS）实验相结合的最新进展。我们简要概述了这些技术提供的不同类型的信息。然后，我们讨论了为整合 NMR 和 SAS 数据而开发的计算方法，特别是考虑到存在动态结构集合和所研究的生物分子的灵活性。最后，介绍了 NMR 和 SAS 成功结合的最新实例，以说明它们结合的实用性。
