Michael Barber Centre for Collaborative Mass Spectrometry, Manchester Institute for Biotechnology, School of Chemistry, University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom.
Michael Barber Centre for Collaborative Mass Spectrometry, Manchester Institute for Biotechnology, School of Chemistry, University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom.
Curr Opin Chem Biol. 2018 Feb;42:177-185. doi: 10.1016/j.cbpa.2018.01.007. Epub 2018 Feb 9.
Entire functional proteins as well as large regions of proteins lack structural elements which are resolvable via crystallography or NMR. These intrinsically disordered proteins (IDPs) or regions (IDRs) are often involved in cell regulation processes, for example in signalling hubs and as a result aberrant behaviour can cause or be representative of disease. As a consequence there is a pressing need to develop alternative structural methods for IDPs and the interactions that they may form with other proteins and/or with potential inhibitors of binding. One such method is ion mobility mass spectrometry (IM-MS) coupled with careful application of electrospray ionisation, which shows great promise as a technique that does not 'care' if a protein is structured or not. We highlight recent work which has employed IM-MS to study conformational heterogeneity in disordered proteins, and discuss the opportunities, as well as the challenges of this approach.
整个功能蛋白以及蛋白质的大片段都缺乏可通过晶体学或 NMR 解析的结构元件。这些固有无序的蛋白质（IDP）或区域（IDR）通常参与细胞调节过程，例如在信号枢纽中，因此异常行为可能导致或代表疾病。因此，迫切需要开发用于 IDP 的替代结构方法，以及它们可能与其他蛋白质和/或潜在的结合抑制剂形成的相互作用。其中一种方法是离子淌度质谱（IM-MS）与精心应用的电喷雾电离相结合，它作为一种不“关心”蛋白质是否具有结构的技术显示出巨大的前景。我们强调了最近使用 IM-MS 研究无序蛋白质构象异质性的工作，并讨论了这种方法的机会和挑战。
