摘要
糖基化是蛋白质翻译后修饰中最为多样和复杂的类型之一,具有广泛且重要的生物学功能.作为研究蛋白质糖基化修饰的核心领域,糖蛋白质组学,尤其是位点特异性糖基化蛋白质组学研究,能够揭示与疾病相关的糖链结构和糖基化位点.这不仅有助于深入理解特定蛋白质糖基化修饰特征,还为揭示糖基化在疾病发生和发展中的作用机制提供了重要的信息.本综述回顾了过去20年基于质谱的糖蛋白质组学的主要进展,重点聚焦于完整糖肽解析的研究成果.首先,概述了糖蛋白质组学的发展历程,并回顾了从糖基化位点鉴定到完整糖肽解析中的关键研究进展.随后,深入探讨了糖肽富集技术、质谱分析方法、数据解析工具及数据库建设等方面的进展,分析了相关技术的优势与挑战.最后,指出了当前糖蛋白质组学研究中亟需解决的问题,并展望了未来在解析深度、全面性、准确性及生物医学应用等方面的发展方向.
Glycosylation is one of the most intricate and variable post-translational modifications(PTMs),playing a pivotal role in various biological processes such as cell signaling,immune response,protein folding,and molecular recognition.The dynamic and diverse nature of glycosylation makes it an essential modification in cellular function and organismal development,as well as in disease progression.Glycoproteomics has emerged as a core field that enables the in-depth analysis of glycoproteins,providing valuable insights into the glycosylation sites and the underlying glycan structures.This is particularly important for understanding how changes in glycosylation patterns are linked to disease states,such as cancer,autoimmune disorders,and neurodegenerative diseases.Over the past two decades,significant advancements in mass spectrometry(MS)-based glycoproteomics have revolutionized the study of protein glycosylation.Initially,the identification of glycosylation sites was primarily based on peptide mapping techniques.However,the field has evolved to focus on the analysis of intact glycopeptides,which preserve both the peptide backbone and the attached glycans,providing a more complete view of glycosylation.The development of cutting-edge MS technologies has enabled researchers to detect and characterize a wide variety of glycopeptides with high sensitivity and specificity.These advancements have allowed for the identification of glycosylation sites at unprecedented levels of detail,unveiling complex glycan structures and modifications that were previously difficult to study.One of the key developments in glycoproteomics has been the enhancement of glycopeptide enrichment methods,which facilitate the isolation of glycosylated peptides from complex biological samples.These techniques,such as lectin affinity chromatography and hydrophilic interaction liquid chromatography(HILIC),have significantly improved the sensitivity and throughput of glycoproteomics analyses.In parallel,advances in mass spectrometry analytical strategies,including high-resolution MS and tandem MS(MS/MS),have provided deeper insights into glycopeptide fragmentation patterns,allowing for the determination of site-specific glycosylation of glycoproteins.Despite these advancements,several challenges remain in glycoproteomics,such as the need for improved analytical depth and reproducibility,the complexity of glycan structures,and the incomplete characterization of low-abundance glycosylated proteins.Furthermore,data interpretation tools and glycan databases are still evolving to keep pace with the growing complexity of glycosylation data.Looking ahead,the future of glycoproteomics will likely involve the development of more accurate,high-throughput methods for glycoprotein analysis,the integration of multi-omics approaches,and the application of glycoproteomics in personalized medicine,particularly for the discovery of biomarkers and therapeutic targets in disease.
作者
陈乐晗
刘佳林
曹纬倩
Lehan Chen;Jialin Liu;Weiqian Cao(Shanghai Fifth People’s Hospital and Institutes of Biomedical Sciences,Fudan University,Shanghai 200032,China;NHC Key Laboratory of Glycoconjugates Research,Fudan University,Shanghai 200032,China)
出处
《科学通报》
北大核心
2025年第15期2302-2318,共17页
Chinese Science Bulletin
基金
国家重点研发计划(2024YFA1306300)
国家自然科学基金面上项目(32271490)资助。
关键词
糖蛋白质组学
位点特异性糖基化解析
完整糖肽鉴定和定量
质谱分析
glycoproteomics
site-specific glycosylation analysis
identification and quantification of intact glycopeptides
mass spectrometry analysis
作者简介
联系人:曹纬倩,E-mail:wqcao@fudan.edu.cn。
