Ion Mobility-Mass Spectrometry and its Applications in Protein Glycosylation Research

Glycosylation is one of the most important post-translational modifications (PTM), mediating physiological processes like cell adhesion, cell proliferation, cell signaling, and immune responses. The special functionality of glycosylation for cancer progression and metastasis were reported in recent...

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Main Authors: FU Bin1, LIANG Yu-ying1, LU Hao-jie1,2
Format: Article
Language:English
Published: Editorial Board of Journal of Chinese Mass Spectrometry Society 2022-09-01
Series:Zhipu Xuebao
Subjects:
Online Access:http://www.jcmss.com.cn/CN/article/openArticlePDF.jsp?attachType=PDF&id=3095
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author FU Bin1
LIANG Yu-ying1
LU Hao-jie1,2
author_facet FU Bin1
LIANG Yu-ying1
LU Hao-jie1,2
author_sort FU Bin1
collection DOAJ
description Glycosylation is one of the most important post-translational modifications (PTM), mediating physiological processes like cell adhesion, cell proliferation, cell signaling, and immune responses. The special functionality of glycosylation for cancer progression and metastasis were reported in recent researches. Analytical methods based on mass spectrometry (MS), especially liquid chromatography mass spectrometry (LC-MS), are the routine practices for protein glycosylation research. However, due to the high complexity and multiformity of glycan structures, as well as the existence of numerous isomers, in-depth analysis of glycosylation ends up as a major challenge for conventional LC-MS-based method. Ion mobility separation is a promising approach to fill the gap as it provides an additional separation dimension for mass spectrometry analysis based on structures and charges of the gas-phase ions. As a technology with an entirely different separation mechanism from that of liquid chromatography, ion mobility spectrometry (IM) has several properties superior to other separation facilities. First of all, unlike liquid chromatography or capillary electrophoresis which demand minutes of separation time, IM only requires a few milliseconds to finish the separation, and it is well compatible with fast mass spectrometry analysis. Besides, as a separation technique for gas phase ions, IM can be modularized and readily integrated into full-fledged LC-MS system. Most importantly, IM is proved to have great potential in glycan isomer discriminations. Given the aforementioned merits, ion mobility mass spectrometry (IM-MS) is gaining attention from glycomics community. This review summarized the basic principles of IM-MS and its applications in protein glycosylation research for the past five years. The means of enhancing isomeric separation performance of glycans were comprehensively discussed, including derivatization, forming metal and other noncovalent adducts, and utilizing high-resolution ion mobility spectrometry implementation. The various approaches of leveraging collision cross section (CCS) values to assist glycan identification and isomer discrimination were also summarized. Furthermore, as two monosaccharides with great biological and pathological significance, the IM-MS applications on fucoses and sialic acids were given special attention. As for glycopeptides, innovative spectra matching algorithms, novel ion activation techniques to facilitate glycan and peptide elucidations, and brand new quantification strategies for isomers were included, along with various glycoproteomic applications of IM-MS on biological samples. Finally, in terms of IM-MS applications in glycoprotein research, investigations of conformational properties, 3D structures, stabilities, and protein-protein interactions were covered. It was concluded that IM-MS is a promising method for protein glycosylation research with great potential.
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spelling doaj.art-4ba80002fe784b2b9d1248a408c483b72022-12-22T04:20:26ZengEditorial Board of Journal of Chinese Mass Spectrometry SocietyZhipu Xuebao1004-29972022-09-0143556457910.7538/zpxb.2022.0083Ion Mobility-Mass Spectrometry and its Applications in Protein Glycosylation ResearchFU Bin10LIANG Yu-ying11LU Hao-jie1,221. Institutes of Biomedical Sciences and Department of Chemistry, Fudan University1. Institutes of Biomedical Sciences and Department of Chemistry, Fudan University1. Institutes of Biomedical Sciences and Department of Chemistry, Fudan University;2. NHC Key Laboratory of Glycoconjugates Research, Fudan UniversityGlycosylation is one of the most important post-translational modifications (PTM), mediating physiological processes like cell adhesion, cell proliferation, cell signaling, and immune responses. The special functionality of glycosylation for cancer progression and metastasis were reported in recent researches. Analytical methods based on mass spectrometry (MS), especially liquid chromatography mass spectrometry (LC-MS), are the routine practices for protein glycosylation research. However, due to the high complexity and multiformity of glycan structures, as well as the existence of numerous isomers, in-depth analysis of glycosylation ends up as a major challenge for conventional LC-MS-based method. Ion mobility separation is a promising approach to fill the gap as it provides an additional separation dimension for mass spectrometry analysis based on structures and charges of the gas-phase ions. As a technology with an entirely different separation mechanism from that of liquid chromatography, ion mobility spectrometry (IM) has several properties superior to other separation facilities. First of all, unlike liquid chromatography or capillary electrophoresis which demand minutes of separation time, IM only requires a few milliseconds to finish the separation, and it is well compatible with fast mass spectrometry analysis. Besides, as a separation technique for gas phase ions, IM can be modularized and readily integrated into full-fledged LC-MS system. Most importantly, IM is proved to have great potential in glycan isomer discriminations. Given the aforementioned merits, ion mobility mass spectrometry (IM-MS) is gaining attention from glycomics community. This review summarized the basic principles of IM-MS and its applications in protein glycosylation research for the past five years. The means of enhancing isomeric separation performance of glycans were comprehensively discussed, including derivatization, forming metal and other noncovalent adducts, and utilizing high-resolution ion mobility spectrometry implementation. The various approaches of leveraging collision cross section (CCS) values to assist glycan identification and isomer discrimination were also summarized. Furthermore, as two monosaccharides with great biological and pathological significance, the IM-MS applications on fucoses and sialic acids were given special attention. As for glycopeptides, innovative spectra matching algorithms, novel ion activation techniques to facilitate glycan and peptide elucidations, and brand new quantification strategies for isomers were included, along with various glycoproteomic applications of IM-MS on biological samples. Finally, in terms of IM-MS applications in glycoprotein research, investigations of conformational properties, 3D structures, stabilities, and protein-protein interactions were covered. It was concluded that IM-MS is a promising method for protein glycosylation research with great potential.http://www.jcmss.com.cn/CN/article/openArticlePDF.jsp?attachType=PDF&id=3095glycosylationion mobility-mass spectrometry (im-ms)post-translational modifications (ptm)glycomicsglycoproteomics
spellingShingle FU Bin1
LIANG Yu-ying1
LU Hao-jie1,2
Ion Mobility-Mass Spectrometry and its Applications in Protein Glycosylation Research
Zhipu Xuebao
glycosylation
ion mobility-mass spectrometry (im-ms)
post-translational modifications (ptm)
glycomics
glycoproteomics
title Ion Mobility-Mass Spectrometry and its Applications in Protein Glycosylation Research
title_full Ion Mobility-Mass Spectrometry and its Applications in Protein Glycosylation Research
title_fullStr Ion Mobility-Mass Spectrometry and its Applications in Protein Glycosylation Research
title_full_unstemmed Ion Mobility-Mass Spectrometry and its Applications in Protein Glycosylation Research
title_short Ion Mobility-Mass Spectrometry and its Applications in Protein Glycosylation Research
title_sort ion mobility mass spectrometry and its applications in protein glycosylation research
topic glycosylation
ion mobility-mass spectrometry (im-ms)
post-translational modifications (ptm)
glycomics
glycoproteomics
url http://www.jcmss.com.cn/CN/article/openArticlePDF.jsp?attachType=PDF&id=3095
work_keys_str_mv AT fubin1 ionmobilitymassspectrometryanditsapplicationsinproteinglycosylationresearch
AT liangyuying1 ionmobilitymassspectrometryanditsapplicationsinproteinglycosylationresearch
AT luhaojie12 ionmobilitymassspectrometryanditsapplicationsinproteinglycosylationresearch