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糖基化:蛋白质的异质性与三维结构

Glycosylation: heterogeneity and the 3D structure of proteins.

作者信息

Rudd P M, Dwek R A

机构信息

Department of Biochemistry, University of Oxford, U.K.

出版信息

Crit Rev Biochem Mol Biol. 1997;32(1):1-100. doi: 10.3109/10409239709085144.

DOI:10.3109/10409239709085144
PMID:9063619
Abstract

Glycoproteins generally exist as populations of glycosylated variants (glycoforms) of a single polypeptide. Although the same glycosylation machinery is available to all proteins that enter the secretory pathway in a given cell, most glycoproteins emerge with characteristic glycosylation patterns and heterogeneous populations of glycans at each glycosylation site. The factors that control the composition of the glycoform populations and the role that heterogeneity plays in the function of glycoproteins are important questions for glycobiology. A full understanding of the implications of glycosylation for the structure and function of a protein can only be reached when a glycoprotein is viewed as a single entity. Individual glycoproteins, by virtue of their unique structures, can selectively control their own glycosylation by modulating interactions with the glycosylating enzymes in the cell. Examples include protein-specific glycosylation within the immunoglobulins and immunoglobulin superfamily and site-specific processing in ribonuclease, Thy-1, IgG, tissue plasminogen activator, and influenza A hemagglutinin. General roles for the range of sugars on glycoproteins such as the leukocyte antigens include orientating the molecules on the cell surface. A major role for specific sugars is in recognition by lectins, including chaperones involved in protein folding. In addition, the recognition of identical motifs in different glycans allows a heterogeneous population of glycoforms to participate in specific biological interactions.

摘要

糖蛋白通常以单个多肽的糖基化变体(糖型)群体形式存在。尽管进入特定细胞分泌途径的所有蛋白质都可利用相同的糖基化机制,但大多数糖蛋白在每个糖基化位点都呈现出特征性的糖基化模式和异质性聚糖群体。控制糖型群体组成的因素以及异质性在糖蛋白功能中所起的作用,是糖生物学中的重要问题。只有将糖蛋白视为一个单一实体,才能全面理解糖基化对蛋白质结构和功能的影响。单个糖蛋白凭借其独特结构,可通过调节与细胞内糖基化酶的相互作用来选择性地控制自身糖基化。实例包括免疫球蛋白和免疫球蛋白超家族内的蛋白质特异性糖基化,以及核糖核酸酶、Thy-1、IgG、组织纤溶酶原激活剂和甲型流感血凝素中的位点特异性加工。糖蛋白上一系列糖类的一般作用,如白细胞抗原,包括在细胞表面定向分子。特定糖类的一个主要作用是被凝集素识别,包括参与蛋白质折叠的伴侣蛋白。此外,在不同聚糖中识别相同基序,使得异质性糖型群体能够参与特定的生物相互作用。

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