Mass spectrometry of transferrin and apolipoprotein C-III for diagnosis and screening of congenital disorder of glycosylation
Mass spectrometry of transferrin and apolipoprotein C-III for diagnosis and screening of congenital disorder of glycosylation
复制标题
转铁蛋白和载脂蛋白 C-III 质谱分析用于诊断和筛查先天性糖基化障碍
作者：
Y. Wada
先天性糖基化障碍（CDG）以前代表一组由于蛋白质 N-糖基化生物合成途径缺陷引起的疾病，目前涵盖了影响糖复合物的多种疾病。自 1992 年首次应用于磷酸甘露糖变位酶 2 缺陷 CDG 患者的血清转铁蛋白以来，质谱 (MS) 在识别和表征影响糖蛋白的糖基化缺陷方面一直发挥着关键作用。天然转铁蛋白的 MS 检测到经典 CDG-I 类型分子异常所特有的聚糖的缺乏。特别是，天然转铁蛋白的电喷雾电离 MS 可以精确分析糖型，但需要有关多电荷离子解卷积的基础知识，多电荷离子在转变为单电荷形式时可能会产生重影信号。对转铁蛋白的胰蛋白酶消化产生的糖肽进行质谱分析，描绘了位点特异性糖型，并揭示了供体/受体底物的微妙平衡或细胞中新生蛋白质的构象效应。载脂蛋白 C-III 的基质辅助激光解吸电离 MS 是一种阐明粘蛋白型核心 1 O-聚糖特征（包括位点占用和糖型）的简单方法。在这篇技术综述中，讨论了 CDG 质谱的原理和缺陷，并介绍了各种类型 CDG 的质谱。
Congenital disorder of glycosylation (CDG), formerly representing a group of diseases due to defects in the biosynthetic pathway of protein N-glycosylation, currently covers a wide range of disorders affecting glycoconjugates. Since its first application to serum transferrin from a CDG patient with phosphomannomutase-2 deficiency in 1992, mass spectrometry (MS) has been playing a key role in identification and characterization of glycosylation defects affecting glycoproteins. MS of native transferrin detects a lack of glycans characteristic to the classical CDG-I type of molecular abnormality. Electrospray ionization MS of native transferrin, especially, allows glycoforms to be analyzed precisely but requires basic knowledge regarding deconvolution of multiply-charged ions which may generate ghost signals upon transformation into a singly-charged form. MS of glycopeptides from tryptic digestion of transferrin delineates site-specific glycoforms and reveals a delicate balance of donor/acceptor substrates or the conformational effect of nascent proteins in cells. Matrix-assisted laser desorption ionization MS of apolipoprotein C-III is a simple method of elucidating the profiles of mucin-type core 1 O-glycans including site occupancy and glycoforms. In this technological review, the principle and pitfalls of MS for CDG are discussed and mass spectra of various types of CDG are presented.
影响因子：
9.8
作者：
Ng, Bobby G.;Buckingham, Kati J.;Freeze, Hudson H.
通讯作者：
Freeze, Hudson H.