蛋白质立体化学修饰的离子淌度质谱研究进展  

Recent Progress in Protein Stereochemical Modifications Revealed by Ion Mobility-Mass Spectrometry

作　　者：许霞 朱致君 李灵军 李功玉 XU Xia;ZHU Zhi-jun;LI Ling-jun;LI Gong-yu(Tianjin Key Laboratory of Biosensing and Molecular Recognition,Research Center for Analytical Science,College of Chemistry,Nankai University,Tianjin 300071,China;School of Pharmacy and Department of Chemistry,University of Wisconsin-Madison,Madison,WI 53705,USA;Haihe Laboratory of Sustainable Chemical Transformations,Tianjin 300192,China)

机构地区：[1]南开大学化学学院分析科学研究中心,天津市生物传感与分子识别重点实验室,天津300071 [2]威斯康星大学麦迪逊分校化学系和药学院,威斯康星州53705 [3]物质绿色创造与制造海河实验室,天津300192

出　　处：《质谱学报》2022年第5期580-595,I0004,共17页Journal of Chinese Mass Spectrometry Society

基　　金：国家自然科学基金(22104064);物质绿色创造与制造海河实验室资助项目;中央高校基本科研业务费专项资金。

摘　　要：蛋白质立体化学修饰是一类低丰度、与人类多种疾病相关的翻译后修饰,由于其并未改变蛋白质的分子质量,难以通过传统的蛋白组学鉴定方法进行发现与鉴定。离子淌度质谱(IM-MS)技术依据不同离子在漂移管中与缓冲气体碰撞后迁移速率的不同而快速分离离子,提供了一种基于构象、电荷数、尺寸和分子质量的分离手段,已在蛋白质立体化学修饰的鉴定与分离分析中取得了阶段性进展。本文从非变性离子淌度质谱实验的角度出发,介绍了漂移管离子淌度仪、行波离子淌度仪、微分迁移率分析仪、高场不对称离子淌度仪以及捕获离子淌度仪等5种商业化离子淌度仪的性能。在此基础上,总结了立体化学修饰高分辨离子淌度质谱分离分析与鉴定方法的最新研究进展,同时介绍了立体化学修饰调控的配体-受体相互作用的结构质谱表征策略,尤其对碰撞诱导去折叠技术在复合物手性构象差异中的研究进行阐述。最后,展望了基于IM-MS的立体化学修饰鉴定与定量等研究方向,以期为立体化学修饰的下一发展阶段提供参考。Protein stereochemical modification(SCM)is a unique type of low-abundance post-translational modification associated with many human diseases.Because it does not change the molecular weight of proteins,traditional proteomics methods are generally not suitable for their discovery and identification.As ions migrate differentially when they collide with the buffer gas in a drift tube,the ions can be separated according to their mass,shape and charge by ion mobility-mass spectrometry(IM-MS),thus providing a means of conformation-based separation,which enables fast identification and separation of protein SCM.In this review,from the perspective of native IM-MS,the performances of five commercial ion mobility analyzers were introduced and compared,including drift tube ion mobility spectrometer,traveling wave ion mobility spectrometer,differential mobility analyzer,high-field asymmetric waveform ion mobility spectrometer,and trapped ion mobility spectrometer.It was focused on the recent advances of the analysis and identification for protein SCM via native IM-MS,and the role of structural MS strategy in the study of SCM effect on ligand-receptor interactions,especially the application of collision-induced unfolding techniques to the conformational study of chirality-regulated neuropeptide-receptor complexes.Finally,the future directions of IM-MS-based SCM identification and quantification were discussed,and guidelines for the next phase study of protein SCM were offered.

关 键 词：离子淌度质谱(IM-MS) 立体化学修饰 D-型突变多肽蛋白 神经肽受体 碰撞诱导去折叠 

分 类 号：O657.63[理学—分析化学]