Mehta A, Lu X, Block T M, Blumberg B S, Dwek R A
The Glycobiology Institute, Department of Biochemistry, Oxford University, United Kingdom.
Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1822-7. doi: 10.1073/pnas.94.5.1822.
The role of N-linked glycosylation and glycan trimming in the function of glycoproteins remains a central question in biology. Hepatitis B virus specifies three glycoproteins (L, M, and S) that are derived from alternate translation of the same ORF. All three glycoproteins contain a common N-glycosylation site in the S domain while M possesses an additional N-glycosylation site at its amino terminus. In the presence of N-butyl-deoxnojirimycin (an inhibitor of alpha-glucosidase) virions and the M protein are surprisingly retained. Preliminary evidence suggests that the retained M protein is hyperglucosylated and localized to lysosomal vesicles. In contrast, the S and L proteins are secreted, and their glycosylation state is unaffected by the presence of the inhibitor. Site-directed mutagenesis provides evidence that virion secretion requires the glycosylation sequon in the pre-S2 domain of M. This highlights the potential role of the M protein oligosaccharide as a therapeutic target.
N-连接糖基化和聚糖修剪在糖蛋白功能中的作用仍然是生物学中的一个核心问题。乙型肝炎病毒指定了三种糖蛋白（L、M和S），它们来自同一开放阅读框的交替翻译。所有三种糖蛋白在S结构域中都含有一个共同的N-糖基化位点，而M在其氨基末端还具有一个额外的N-糖基化位点。在存在N-丁基-脱氧野尻霉素（一种α-葡萄糖苷酶抑制剂）的情况下，病毒粒子和M蛋白出人意料地被保留下来。初步证据表明，保留的M蛋白是高糖基化的，并定位于溶酶体囊泡。相比之下，S和L蛋白被分泌，它们的糖基化状态不受抑制剂存在的影响。定点诱变提供了证据，表明病毒粒子分泌需要M的前S2结构域中的糖基化序列。这突出了M蛋白寡糖作为治疗靶点的潜在作用。
