Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455; email:
Annu Rev Biophys. 2017 May 22;46:317-336. doi: 10.1146/annurev-biophys-070816-033701. Epub 2017 Mar 17.
Nuclear magnetic resonance (NMR) spectroscopy has been instrumental during the past two decades in providing high-resolution structures of protein complexes. It has been the method of choice for determining the structure of dynamic protein complexes, which are typically recalcitrant to other structural techniques. Until recently, NMR spectroscopy has yielded structures of small or medium-sized protein complexes, up to approximately 30-40 kDa. Major breakthroughs during the past decade, especially in isotope-labeling techniques, have enabled NMR characterization of large protein systems with molecular weights of hundreds of kDa. This has provided unique insights into the binding, dynamic, and allosteric properties of large systems. Notably, there is now a slowly but steadily growing list of large, dynamic protein complexes whose atomic structure has been determined by NMR. Many of these complexes are characterized by a high degree of flexibility and, thus, their structures could not have been obtained using other structural methods. Especially in the field of molecular chaperones, NMR has recently provided the first-ever high-resolution structures of their complexes with unfolded proteins. Further technological advances will establish NMR as the primary tool for obtaining atomic structures of challenging systems with even higher complexity.
在过去的二十年中，核磁共振（NMR）光谱学在提供蛋白质复合物的高分辨率结构方面发挥了重要作用。它是确定动态蛋白质复合物结构的首选方法，而这些复合物通常对其他结构技术具有抗性。直到最近，NMR 光谱学才能够确定小至中等大小的蛋白质复合物的结构，分子量约为 30-40 kDa。过去十年中的重大突破，尤其是在同位素标记技术方面，使得能够对分子量达数百 kDa 的大型蛋白质系统进行 NMR 表征。这为大型系统的结合、动态和变构特性提供了独特的见解。值得注意的是，现在有一个缓慢但稳定增长的大型动态蛋白质复合物列表，其原子结构已通过 NMR 确定。这些复合物中的许多都具有高度的灵活性，因此，它们的结构无法通过其他结构方法获得。特别是在分子伴侣领域，NMR 最近提供了其与未折叠蛋白质复合物的首个高分辨率结构。进一步的技术进步将使 NMR 成为获得具有更高复杂性的挑战性系统的原子结构的主要工具。
