Beveridge Rebecca, Calabrese Antonio N
Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow, United Kingdom.
Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
Front Chem. 2021 Mar 11;9:603639. doi: 10.3389/fchem.2021.603639. eCollection 2021.
Intrinsically disordered proteins (IDPs) and regions of intrinsic disorder (IDRs) are abundant in proteomes and are essential for many biological processes. Thus, they are often implicated in disease mechanisms, including neurodegeneration and cancer. The flexible nature of IDPs and IDRs provides many advantages, including (but not limited to) overcoming steric restrictions in binding, facilitating posttranslational modifications, and achieving high binding specificity with low affinity. IDPs adopt a heterogeneous structural ensemble, in contrast to typical folded proteins, making it challenging to interrogate their structure using conventional tools. Structural mass spectrometry (MS) methods are playing an increasingly important role in characterizing the structure and function of IDPs and IDRs, enabled by advances in the design of instrumentation and the development of new workflows, including in native MS, ion mobility MS, top-down MS, hydrogen-deuterium exchange MS, crosslinking MS, and covalent labeling. Here, we describe the advantages of these methods that make them ideal to study IDPs and highlight recent applications where these tools have underpinned new insights into IDP structure and function that would be difficult to elucidate using other methods.
内在无序蛋白质（IDP）和内在无序区域（IDR）在蛋白质组中大量存在，对许多生物过程至关重要。因此，它们常常与包括神经退行性变和癌症在内的疾病机制有关。IDP和IDR的柔性本质具有诸多优势，包括（但不限于）克服结合中的空间位阻限制、促进翻译后修饰以及以低亲和力实现高结合特异性。与典型的折叠蛋白不同，IDP采用异质性结构集合，这使得使用传统工具研究其结构具有挑战性。结构质谱（MS）方法在表征IDP和IDR的结构与功能方面发挥着越来越重要的作用，这得益于仪器设计的进步以及新工作流程的开发，包括原生质谱、离子淌度质谱、自上而下质谱、氢氘交换质谱、交联质谱和共价标记。在此，我们描述这些方法的优势，这些优势使其成为研究IDP的理想选择，并突出近期的应用，其中这些工具为IDP结构和功能带来了新见解，而这些见解使用其他方法难以阐明。
