NMR spectroscopy is a powerful tool for the investigation of protein folding and misfolding, providing a characterization of molecular structure, dynamics and exchange processes, across a very wide range of timescales and with near atomic resolution. In recent years NMR methods have also been developed to study protein folding as it might occur within the cell, in a de novo manner, by observing the folding of nascent polypeptides in the process of emerging from the ribosome during synthesis. Despite the 2.3 MDa molecular weight of the bacterial 70S ribosome, many nascent polypeptides, and some ribosomal proteins, have sufficient local flexibility that sharp resonances may be observed in solution-state NMR spectra. In providing information on dynamic regions of the structure, NMR spectroscopy is therefore highly complementary to alternative methods such as X-ray crystallography and cryo-electron microscopy, which have successfully characterized the rigid core of the ribosome particle. However, the low working concentrations and limited sample stability associated with ribosome-nascent chain complexes means that such studies still present significant technical challenges to the NMR spectroscopist. This review will discuss the progress that has been made in this area, surveying all NMR studies that have been published to date, and with a particular focus on strategies for improving experimental sensitivity.

中文翻译：

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使用核磁共振光谱研究核糖体上的蛋白质折叠

核磁共振波谱是研究蛋白质折叠和错误折叠的有力工具，可提供分子结构、动力学和交换过程的表征，跨越非常广泛的时间尺度和接近原子的分辨率。近年来，还开发了 NMR 方法来研究蛋白质折叠，因为它可能以从头的方式在细胞内发生，通过观察合成期间从核糖体出现的过程中新生多肽的折叠。尽管细菌 70S 核糖体的分子量为 2.3 MDa，但许多新生多肽和一些核糖体蛋白具有足够的局部灵活性，可以在溶液状态 NMR 光谱中观察到尖锐的共振。在提供有关结构动态区域的信息时，因此，NMR 光谱学与 X 射线晶体学和低温电子显微镜等替代方法高度互补，这些方法已成功表征了核糖体颗粒的刚性核心。然而，与核糖体-新生链复合物相关的低工作浓度和有限的样品稳定性意味着此类研究仍然对 NMR 光谱学家提出了重大的技术挑战。这篇综述将讨论在这一领域取得的进展，调查迄今为止已发表的所有 NMR 研究，并特别关注提高实验灵敏度的策略。与核糖体-新生链复合物相关的低工作浓度和有限的样品稳定性意味着此类研究仍然对 NMR 光谱学家提出了重大的技术挑战。这篇综述将讨论在这一领域取得的进展，调查迄今为止已发表的所有 NMR 研究，并特别关注提高实验灵敏度的策略。与核糖体-新生链复合物相关的低工作浓度和有限的样品稳定性意味着此类研究仍然对 NMR 光谱学家提出了重大的技术挑战。这篇综述将讨论在这一领域取得的进展，调查迄今为止已发表的所有 NMR 研究，并特别关注提高实验灵敏度的策略。