Recent progress of protein glycosylation characterization utilizing native conformer-resolved mass spectrometry

JIA Yifei; WANG Yamei; LI Gongyu

doi:10.11665/j.issn.1000-5048.2023060901

Journal of China Pharmaceutical University > 2023 > 54(6): 674-681. > DOI: 10.11665/j.issn.1000-5048.2023060901

JIA Yifei, WANG Yamei, LI Gongyu. Recent progress of protein glycosylation characterization utilizing native conformer-resolved mass spectrometry[J]. Journal of China Pharmaceutical University, 2023, 54(6): 674-681. DOI: 10.11665/j.issn.1000-5048.2023060901

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Recent progress of protein glycosylation characterization utilizing native conformer-resolved mass spectrometry

1.
Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Science, College of Chemistry, Nankai University, Tianjin 300071
2.
Haihe Laboratory of Sustainable Chemical Transformations, Tianjin 300192, China

Funds: This study was supported by the National Natural Science Foundation of China (No.22104064, No.22293030, No.22293032) and the National Key R&D Program of China (No.2022YFA1305200)

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Received Date: June 08, 2023
Revised Date: July 17, 2023

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Abstract

Abstract

Glycosylation of proteins, one of the most prevalent and complex post-translational modifications occurring in nature, plays a crucial role in regulating protein net charge, conformation, binding properties and, ultimately, biological function.Traditional structural techniques are not amenable for glycoproteins due to the inherent heterogeneity of oligosaccharides.With the advances in analytical technique, mass spectrometry displays an increasingly crucial role in elucidating the structure of glycoproteins.Mass spectrometry-based proteomic technique can dissect the chemical composition and site information of low-abundance glycosylation at the peptide level.Instead, native mass spectrometry (nMS) can analyze intact glycoproteins while maintaining the information for glycan heterogeneity, and the insights into the regulatory effects of glycosylation on protein higher order structures and interactions with other proteins or ligands.As a representative structural mass spectrometry tool, ion mobility-based nMS strategy is powered by its conformer-resolving capability and by the feasibility of conformer manipulation through collision-induced unfolding.Consequently, native IM-MS analysis can provide rich information of dynamic protein conformations, allowing for the rapid identification and differentiation of protein isoforms in an unprecedented manner.In this review, we briefly introduced two emerging native IM-MS analytical modes, dynamic conformer-resolving mode and glycoform-resolving mode.Besides, we also discussed the recent progress of conformational and topological characterization of intact glycoproteins with three typical model systems based on two above-mentioned emerging modes of native IM-MS.

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References (53)

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