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Epitope structure of the carbohydrate recognition domain of asialoglycoprotein receptor to a monoclonal antibody revealed by proteolytic excision mass spectrometry

机译:蛋白质水解切除质谱透析蛋白质糖蛋白受体的碳水化合物识别结构域的表位结构蛋白水解切除质谱显示的单克隆抗体

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The asialoglycoprotein receptor (ASGP-R) belongs to the C-type (calcium-dependent) class of lectins and is located on hepatocytes of all mammalian organisms [1]. The receptor is a hetero-oligomer of two homologous subunits H1 and H2, each containing a C-terminal carbohydrate recognition domain. The carbohydrate recognition domain of subunit H1 (H1-CRD) provides clearance of circulating glycoproteins. with terminal galactose and N-acetylgalactosamine. Recent studies suggest that the carbohydrate recognition domain of the asialoglycoprotein receptor (H1-CRD) is used as entry site into hepatocytes by hepatitis A, hepatitis B, and Marburg viruses [2]. Thus, molecules binding specifically to the CRD might have inhibitory effects on the virus entry. In this study, the epitope to a monoclonal antibody against H1-CRD was elucidated by proteolytic epitope excision in combination with high resolution mass spectrometry. Moreover, detailed structural data of the antigen were provided by high resolution mass spectrometric analysis of the intact protein and proteolytic digestion mixtures.
机译:Asialogloticin受体(ASGP-R)属于凝集素的C型(依赖依赖性)类,并且位于所有哺乳动物生物的肝细胞上[1]。受体是两个同源亚基H1和H 2的杂寡端聚合物,其每种含有C末端碳水化合物识别结构域。亚基H1(H1-CRD)的碳水化合物识别结构域提供循环糖蛋白的间隙。用末端半乳糖和N-乙酰甘乳酰胺。最近的研究表明,唾液酸糖蛋白受体(H1-CRD)的糖识别结构域被用作进入位点到由A型肝炎,B型肝炎的肝细胞,病毒和马尔堡病毒[2]。因此,特异性结合CRD的分子可能对病毒进入具有抑制作用。在该研究中,通过蛋白水解表位切除与高分辨率质谱结合阐明了对H1-CRD的单克隆抗体的表位。此外,通过对完整蛋白质和蛋白水解消化混合物的高分辨率质谱分析提供抗原的详细结构数据。

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