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无定形蛋白质及其与配体复合物的气相构象:从溶液转移到气相过程中的动力学捕获态。

Gas-phase conformations of intrinsically disordered proteins and their complexes with ligands: Kinetically trapped states during transfer from solution to the gas phase.

机构信息

Department of Chemistry, Korea University, Seoul, 02841, Republic of Korea.

Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, 92093.

出版信息

Mass Spectrom Rev. 2019 Nov;38(6):483-500. doi: 10.1002/mas.21596. Epub 2019 Apr 25.

DOI:10.1002/mas.21596
PMID:31021441
Abstract

Flexible structures of intrinsically disordered proteins (IDPs) are crucial for versatile functions in living organisms, which involve interaction with diverse partners. Electrospray ionization ion mobility mass spectrometry (ESI-IM-MS) has been widely applied for structural characterization of apo-state and ligand-associated IDPs via two-dimensional separation in the gas phase. Gas-phase IDP structures have been regarded as kinetically trapped states originated from conformational features in solution. However, an implication of the states remains elusive in the structural characterization of IDPs, because it is unclear what structural property of IDPs is preserved. Recent studies have indicated that the conformational features of IDPs in solution are not fully reproduced in the gas phase. Nevertheless, the molecular interactions captured in the gas phase amplify the structural differences between IDP conformers. Therefore, an IDP conformational change that is not observed in solution is observable in the gas-phase structures obtained by ESI-IM-MS. Herein, we have presented up-to-date researches on the key implications of kinetically trapped states in the gas phase with a brief summary of the structural dynamics of IDPs in ESI-IM-MS.

摘要

无规卷曲蛋白质(IDPs)的柔性结构对生物体内的多功能性至关重要,涉及与多种伴侣的相互作用。电喷雾电离离子淌度质谱(ESI-IM-MS)已广泛应用于通过气相中的二维分离来对 apo 状态和配体结合的 IDPs 进行结构表征。气相 IDP 结构被认为是动力学捕获的状态,源于溶液中的构象特征。然而,在 IDP 的结构表征中,这些状态的含义仍然难以捉摸,因为不清楚 IDP 保留了什么结构特性。最近的研究表明,IDPs 在溶液中的构象特征在气相中不能完全重现。然而,在气相中捕获的分子相互作用放大了 IDP 构象体之间的结构差异。因此,在溶液中观察不到的 IDP 构象变化可以在通过 ESI-IM-MS 获得的气相结构中观察到。本文综述了 ESI-IM-MS 中 IDPs 结构动力学的最新研究进展,阐述了气相中动力学捕获态的关键影响。

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