Tandem trapped ion mobility spectrometry
Tandem trapped ion mobility spectrometry
复制标题
DOI：
10.1039/c7an02054f
复制
发表时间：
2018-05-21
期刊：
影响因子：
4.2
通讯作者：
Bleiholder, Christian
中科院分区：
文献类型：
--
作者：
Liu, Fanny C.;Ridgeway, Mark E.;Bleiholder, Christian
目前，人们对使用离子迁移谱-质谱（IMS-MS）仪器进行结构生物学研究产生了浓厚的兴趣。在这些应用中，来自IMS-MS测量的动量传递截面被用于重建三维分析物结构。最近的报告表明，额外的结构信息可以从测量响应于分析物结构的变化的横截面的变化中提取。为了进一步这种方法，我们构建了一个串联捕获IMS分析仪（TIMS-TIMS），并将其纳入QqTOF质谱仪。TIMS-TIMS是由两个TIMS分析器通过由两个孔组成的“接口区域”耦合而构成的。我们表明，肽低聚物（缓激肽）和nattve样蛋白（ubiqurtin）离子可以通过在TIMS-TIMS分析仪的实验过程中保存。我们展示了碰撞激活以及捕获迁移率选择离子的能力，随后进行迁移率分析。除了诱导构象变化，我们表明，我们可以片段低电荷状态的泛素在> 1毫巴之间的TIMS分析仪具有显着的序列覆盖。许多碎片离子在其TIMS光谱中表现出多种特征，这意味着它们通常可能不作为最稳定的异构体存在。TIMS-TIMS解离迁移率选择的蛋白质离子和测量其碎片离子的横截面的能力为基于IMS的结构阐明开辟了新的可能性。
There is currently a strong interest in the use of ion mobility spectrometry-mass spectrometry (IMS-MS) instrumentation for structural biology. In these applications, momentum transfer cross sections derived from IMS-MS measurements are used to reconstruct the three-dimensional analyte structure. Recent reports indicate that additional structural information can be extracted from measuring changes in cross sections in response to changes of the analyte structure. To further this approach, we constructed a tandem trapped IMS analyser (TIMS-TIMS) and incorporated it in a QqTOF mass spectrometer. TIMS-TIMS is constructed by coupling two TIMS analysers via an "interface region" composed of two apertures. We show that peptide oligomers (bradykinin) and nattve-like protein (ubiqurtin) ions can be preserved through the course of an experiment in a TIMS-TIMS analyser. We demonstrate the ability to collisionally-activate as well as to trap mobility-selected ions, followed by subsequent mobility-analysis. In addition to inducing conformational changes, we show that we can fragment low charge states of ubiquitin at > 1 mbar between the TIMS analysers with significant sequence coverage. Many fragment ions exhibit multiple features in their TIMS spectra, which means that they may not generally exist as the most stable isomer. The ability of TIMS-TIMS to dissociate mobility-selected protein ions and to measure the cross sections of their fragment ions opens new possibilities for IMS-based structure elucidation.