Chow Vimanda, Wolf Esther, Lento Cristina, Wilson Derek J
Department of Chemistry, York University, Toronto, ON M3J 1P3, Canada.
Essays Biochem. 2023 Mar 29;67(2):165-174. doi: 10.1042/EBC20220174.
Biological macromolecules, such as proteins, nucleic acids, and carbohydrates, contain heteroatom-bonded hydrogens that undergo exchange with solvent hydrogens on timescales ranging from microseconds to hours. In hydrogen-deuterium exchange mass spectrometry (HDX-MS), this exchange process is used to extract information about biomolecular structure and dynamics. This minireview focuses on millisecond timescale HDX-MS measurements, which, while less common than 'conventional' timescale (seconds to hours) HDX-MS, provide a unique window into weakly structured species, weak (or fast cycling) binding interactions, and subtle shifts in conformational dynamics. This includes intrinsically disordered proteins and regions (IDPs/IDRs) that are associated with cancer and amyloidotic neurodegenerative disease. For nucleic acids and carbohydrates, structures such as isomers, stems, and loops, can be elucidated and overall structural rigidity can be assessed. We will provide a brief overview of technical developments in rapid HDX followed by highlights of various applications, emphasising the importance of broadening the HDX timescale to improve throughput and to capture a wider range of function-relevant dynamic and structural shifts.
生物大分子，如蛋白质、核酸和碳水化合物，含有与杂原子相连的氢，这些氢会在从微秒到数小时的时间尺度上与溶剂中的氢发生交换。在氢-氘交换质谱法（HDX-MS）中，这种交换过程被用于提取有关生物分子结构和动力学的信息。本综述聚焦于毫秒时间尺度的HDX-MS测量，虽然它不如“传统”时间尺度（数秒到数小时）的HDX-MS常见，但它为研究弱结构化物种、弱（或快速循环）结合相互作用以及构象动力学的细微变化提供了一个独特的窗口。这包括与癌症和淀粉样神经退行性疾病相关的内在无序蛋白质和区域（IDP/IDR）。对于核酸和碳水化合物，可以阐明诸如异构体、茎和环等结构，并评估整体结构刚性。我们将简要概述快速HDX的技术发展，随后重点介绍各种应用，强调拓宽HDX时间尺度以提高通量并捕捉更广泛的与功能相关的动态和结构变化的重要性。
