King's College London , Department of Chemistry, Britannia House, 7 Trinity Street, London SE1 1DB, U.K.
VIB Structural Biology Research Centre (SBRC), Vrije Universiteit Brussel , Pleinlaan 2, Brussels B-1050, Belgium.
J Am Chem Soc. 2015 Nov 4;137(43):13807-17. doi: 10.1021/jacs.5b06027. Epub 2015 Oct 27.
Intrinsically disordered proteins (IDPs) are important for health and disease, yet their lack of net structure precludes an understanding of their function using classical methods. Gas-phase techniques provide a promising alternative to access information on the structure and dynamics of IDPs, but the fidelity to which these methods reflect the solution conformations of these proteins has been difficult to ascertain. Here we use state of the art ensemble techniques to investigate the solution to gas-phase transfer of a range of different IDPs. We show that IDPs undergo a vast conformational space expansion in the absence of solvent to sample a conformational space 3-5 fold broader than in solution. Moreover, we show that this process is coupled to the electrospray ionization process, which brings about the generation of additional subpopulations for these proteins not observed in solution due to competing effects on protein charge and shape. Ensemble methods have permitted a new definition of the solution to gas-phase transfer of IDPs and provide a roadmap for future investigations into flexible systems by mass spectrometry.
无规蛋白（IDPs）在健康和疾病中起着重要作用，但由于其缺乏净结构，使用经典方法来理解其功能是不可能的。气相技术为获取 IDP 结构和动力学信息提供了一种很有前途的替代方法，但这些方法反映这些蛋白质在溶液中的构象的逼真度一直难以确定。在这里，我们使用最先进的集合技术来研究一系列不同 IDP 的气相转移到溶液中的情况。我们表明，在没有溶剂的情况下，IDP 会经历巨大的构象空间扩展，以在溶液中采样 3-5 倍更广泛的构象空间。此外，我们还表明，这一过程与电喷雾电离过程相耦合，由于对蛋白质电荷和形状的竞争效应，导致这些蛋白质产生了在溶液中观察不到的额外亚群。集合方法为 IDP 的溶液到气相转移提供了一个新的定义，并为通过质谱法对灵活系统的未来研究提供了路线图。
