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作 者:Ming Bi Zhixin Tian
机构地区:[1]School of Chemical Science and Engineering,Tongji University,Shanghai 200092,China
出 处:《Acta Biochimica et Biophysica Sinica》2024年第8期1172-1183,共12页生物化学与生物物理学报(英文版)
基 金:supported by the grants from the National Natural Science Foundation of China(Nos.22074105 and 21775110);the Shanghai Science and Technology Commission(No.14DZ2261100).
摘 要:N-linked glycosylation is a common posttranslational modification of proteins that results in macroheterogeneity of the modification site.However,unlike simpler modifications,N-glycosylation introduces an additional layer of complexity with tens of thousands of possible structures arising from various dimensions,including different monosaccharide compositions,sequence structures,linking structures,isomerism,and three-dimensional conformations.This results in additional microheterogeneity of the modification site of N-glycosylation,i.e.,the same N-glycosylation site can be modified with different glycans with a certain stoichiometric ratio.N-glycosylation regulates the structure and function of N-glycoproteins in a site-and structure-specific manner,and differential expression of N-glycosylation under disease conditions needs to be characterized through site-and structurespecific quantitative analysis.Numerous advanced methods ranging from sample preparation to mass spectrum analysis have been developed to distinguish N-glycan structures.Chemical derivatization of monosaccharides,online liquid chromatography separation and ion mobility spectrometry enable the physical differentiation of samples.Tandem mass spectrometry further analyzes the macro/microheterogeneity of intact N-glycopeptides through the analysis of fragment ions.Moreover,the development of search engines and AI-based software has enhanced our understanding of the dissociation patterns of intact N-glycopeptides and the clinical significance of differentially expressed intact N-glycopeptides.With the help of these modern methods,structure-specific N-glycoproteomics has become an important tool with extensive applications in the biomedical field.
关 键 词:N-GLYCOSYLATION N-glycoproteomics mass spectrometry structure specific biomedical application
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