Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA.
Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.
Trends Biochem Sci. 2020 Oct;45(10):906-918. doi: 10.1016/j.tibs.2020.05.005. Epub 2020 May 30.
Methodological improvements in both single particle cryo-electron microscopy (cryo-EM) and hydrogen/deuterium exchange mass spectrometry (HDX-MS) mean that the two methods are being more frequently used together to tackle complex problems in structural biology. There are many benefits to this combination, including for the analysis of low-resolution density, for structural validation, in the analysis of individual proteins versus the same proteins in large complexes, studies of allostery, protein quality control during cryo-EM construct optimization, and in the study of protein movements/dynamics during function. As will be highlighted in this review, through careful considerations of potential sample and conformational heterogeneity, many joint studies have recently been demonstrated, and many future studies using this combination are anticipated.
方法学的改进,无论是在单颗粒冷冻电子显微镜(cryo-EM)还是氢/氘交换质谱(HDX-MS)方面,都意味着这两种方法越来越频繁地被一起用于解决结构生物学中的复杂问题。这种组合有很多好处,包括对低分辨率密度的分析、结构验证、对单个蛋白质与大复合物中相同蛋白质的分析、变构研究、在冷冻电子显微镜构建优化过程中的蛋白质质量控制,以及在功能过程中研究蛋白质的运动/动力学。正如本文综述所强调的,通过对潜在的样品和构象异质性的仔细考虑,最近已经证明了许多联合研究,并且预计未来将有许多使用这种组合的研究。