Characterization of Amyloid Oligomers by Electrospray Ionization-Ion Mobility Spectrometry-Mass Spectrometry (ESI-IMS-MS).

Characterization of Amyloid Oligomers by Electrospray Ionization-Ion Mobility Spectrometry-Mass Spectrometry (ESI-IMS-MS).
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通过电喷雾电离-离子淌度光谱-质谱 (ESI-IMS-MS) 表征淀粉样蛋白低聚物。

DOI:
10.1007/978-1-4939-2978-8_8
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发表时间:
2016
期刊:
Methods in molecular biology (Clifton, N.J.)
影响因子:
--
通讯作者:
Scarff CA
Scarff CA
中科院分区:
--
文献类型:
--
作者:
Scarff CA

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在淀粉样蛋白生成肽和蛋白质种类的自组装过程中形成的可溶性寡聚体通常被认为是高毒性的。因此,这些物种的彻底表征是非常感兴趣的寻求有效的治疗和增强了解淀粉样蛋白纤维化途径。然而,寡聚物的结构表征是具有挑战性的,因为它们通常是短暂的,低密度的,并且高度异质。电喷雾电离-离子迁移谱-质谱(ESI-IMS-MS)是一种强大的技术,其能够检测复杂非均相混合物中的单个离子种类,并根据形状、化学计量、配体结合能力和相对稳定性对其进行表征。在此,我们描述了使用ESI-IMS-MS通过使用数据校准和模型推导来表征β-2-微球蛋白寡聚体的大小和形状。这使得关于淀粉样蛋白形成途径中聚集的寡聚物种类的范围和寡聚物生长模式的信息能够被获得。
Soluble oligomers formed during the self-assembly of amyloidogenic peptide and protein species are generally thought to be highly toxic. Consequently, thorough characterization of these species is of much interest in the quest for effective therapeutics and for an enhanced understanding of amyloid fibrillation pathways. The structural characterization of oligomeric species, however, is challenging as they are often transiently and lowly populated, and highly heterogeneous. Electrospray ionization-ion mobility spectrometry-mass spectrometry (ESI-IMS-MS) is a powerful technique which is able to detect individual ion species populated within a complex heterogeneous mixture and characterize them in terms of shape, stoichiometry, ligand binding capability, and relative stability. Herein, we describe the use of ESI-IMS-MS to characterize the size and shape of oligomers of beta-2-microglobulin through use of data calibration and the derivation of models. This enables information about the range of oligomeric species populateden routeto amyloid formation and the mode of oligomer growth to be obtained.
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