Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198 Gif-sur-Yvette, France.
Chem Rev. 2022 May 25;122(10):9497-9570. doi: 10.1021/acs.chemrev.1c00937. Epub 2022 Mar 31.
In-cell structural biology aims at extracting structural information about proteins or nucleic acids in their native, cellular environment. This emerging field holds great promise and is already providing new facts and outlooks of interest at both fundamental and applied levels. NMR spectroscopy has important contributions on this stage: It brings information on a broad variety of nuclei at the atomic scale, which ensures its great versatility and uniqueness. Here, we detail the methods, the fundamental knowledge, and the applications in biomedical engineering related to in-cell structural biology by NMR. We finally propose a brief overview of the main other techniques in the field (EPR, smFRET, cryo-ET, etc.) to draw some advisable developments for in-cell NMR. In the era of large-scale screenings and deep learning, both accurate and qualitative experimental evidence are as essential as ever to understand the interior life of cells. In-cell structural biology by NMR spectroscopy can generate such a knowledge, and it does so at the atomic scale. This review is meant to deliver comprehensive but accessible information, with advanced technical details and reflections on the methods, the nature of the results, and the future of the field.
细胞内结构生物学旨在提取蛋白质或核酸在其自然细胞环境中的结构信息。这个新兴领域具有巨大的潜力，已经在基础和应用层面提供了新的事实和观点。NMR 光谱学在这一阶段做出了重要贡献：它在原子尺度上提供了广泛的原子核信息，这确保了它的多功能性和独特性。在这里，我们详细介绍了与 NMR 相关的细胞内结构生物学的方法、基础知识和在生物医学工程中的应用。最后，我们简要概述了该领域的主要其他技术（EPR、smFRET、低温电子断层扫描等），以提出一些可行的细胞内 NMR 发展建议。在大规模筛选和深度学习的时代，准确和定性的实验证据与以往一样重要，有助于了解细胞的内部生活。NMR 光谱学的细胞内结构生物学可以提供这样的知识，而且是在原子尺度上。这篇综述旨在提供全面而易于理解的信息，包括先进的技术细节以及对方法、结果性质和该领域未来的思考。
