Structural Proteomics Methods to Interrogate the Conformations and Dynamics of Intrinsically Disordered Proteins.
Structural Proteomics Methods to Interrogate the Conformations and Dynamics of Intrinsically Disordered Proteins.
复制标题
结构蛋白质组学方法来探究内含子无序蛋白质的构象和动力学。
DOI：
10.3389/fchem.2021.603639
复制
发表时间：
2021
影响因子：
5.5
通讯作者：
Calabrese AN
中科院分区：
文献类型：
--
作者：
Beveridge R;Calabrese AN
内源性无序蛋白（IDP）和内源性无序区（IDR）在蛋白质组中大量存在，是许多生物过程所必需的。因此，它们通常与疾病机制有关，包括神经变性和癌症。IDP和IDR的柔性性质提供了许多优点，包括（但不限于）克服结合中的空间限制，促进翻译后修饰，以及以低亲和力实现高结合特异性。与典型的折叠蛋白相比，IDP采用异质结构系综，使得使用常规工具询问其结构具有挑战性。结构质谱（MS）方法在表征IDP和IDR的结构和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和新工作流程的开发，包括天然MS、离子迁移率MS、自上而下MS、氢氘交换MS、交联MS和共价标记。在这里，我们描述了这些方法的优点，使他们理想的研究IDP和突出最近的应用程序，这些工具已经巩固了新的见解IDP的结构和功能，将难以阐明使用其他方法。
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.