Inherent disorder is an integral part of all proteomes, represented as fully or partially unfolded proteins. The lack of order in intrinsically disordered proteins (IDPs) results in an incredibly flexible, floppy, and heterogeneous ensemble, contrary to the well‐structured and unique organization of folded proteins. Despite such unusual demeanor, IDPs are crucial for numerous cellular processes and are increasingly being associated with disease‐causing pathologies. These warrant more intensive investigation of this atypical class of protein. Traditional biophysical tools, however, fall short of analyzing IDPs, thus making their structure‐function characterization challenging. Mass spectrometry (MS) in recent years has evolved as a valuable tool for elucidating the unusual conformational facets of IDPs. In this review, the features of advanced MS techniques such as Hydrogen‐deuterium exchange (HDX)‐MS, native MS, limited proteolysis (LiP)‐MS, chemical cross‐linking (XL)‐MS, and Fast photochemical oxidation of proteins (FPOP)‐MS are briefly discussed. Recent MS studies on IDPs and the unique advantages/shortfalls associated with the above methods while evaluating structural proteomics of IDPs, are illustrated. Eventually the future scope of the MS methods in further decoding the unexplored landscapes of IDPs is presented.

中文翻译：

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基于质谱的结构蛋白质组学在阐明蛋白质内在紊乱中的新作用

固有障碍是所有蛋白质组的组成部分，表现为完全或部分未折叠的蛋白质。内在无序蛋白质 (IDP) 中缺乏秩序会导致非常灵活、松散和异质的整体，这与折叠蛋白质的结构良好且独特的组织相反。尽管有这种不寻常的举止，但 IDP 对许多细胞过程至关重要，并且越来越多地与致病病理相关。这些值得对这种非典型蛋白质进行更深入的研究。然而，传统的生物物理工具无法分析 IDP，从而使其结构功能表征具有挑战性。近年来，质谱 (MS) 已发展成为阐明 IDP 异常构象方面的宝贵工具。在这次审查中，氢-氘交换 (HDX)-MS、天然 MS、有限蛋白水解 (LiP)-MS、化学交联 (XL)-MS 和蛋白质快速光化学氧化 (FPOP)-MS 等先进 MS 技术的特点进行了简要讨论。说明了最近对 IDP 的 MS 研究以及与上述方法相关的独特优势/不足，同时评估了 IDP 的结构蛋白质组学。最后介绍了 MS 方法在进一步解码 IDP 未开发景观方面的未来范围。说明了最近对 IDP 的 MS 研究以及与上述方法相关的独特优势/不足，同时评估了 IDP 的结构蛋白质组学。最后介绍了 MS 方法在进一步解码 IDP 未开发景观方面的未来范围。说明了最近对 IDP 的 MS 研究以及与上述方法相关的独特优势/不足，同时评估了 IDP 的结构蛋白质组学。最后介绍了 MS 方法在进一步解码 IDP 未开发景观方面的未来范围。