Membrane cofactor protein with different types of N-glycans can serve as measles virus receptor.
Membrane cofactor protein with different types of N-glycans can serve as measles virus receptor.
复制标题
具有不同类型N-聚糖的膜辅因子蛋白可以作为麻疹病毒受体。
作者：
A. Maisner;G. Herrler
膜辅因子蛋白（MCP）已被证明是麻疹病毒的细胞受体。在之前的结合研究中，我们证实了麻疹病毒H蛋白与MCP之间的直接相互作用。结果表明，这种结合不依赖于o -聚糖，而依赖于MCP的n -聚糖。为了阐明n -聚糖在MCP受体功能中的作用，我们分析了糖基化抑制剂tunicamycin （TM）和1-脱氧甘露诺吉霉素（DMJ）的作用。据报道，阻止n -糖基化的TM可抑制功能性麻疹病毒受体的表达。在这里，我们发现在Vero细胞表面可以检测到缺乏所有n -聚糖的MCP，尽管数量有所减少。因此，受体活性的缺乏不能用细胞内降解或运输缺陷来解释。在甘露糖苷酶I抑制剂DMJ的存在下，MCP是由高甘露糖型的n -聚糖合成的，而非未经处理的细胞MCP上存在的复合寡糖。在体外结合实验中，富甘露糖MCP和复合n -聚糖MCP均能被麻疹病毒H蛋白识别。它们都可以作为培养的Vero细胞感染的受体，反对病毒与MCP n -聚糖内的碳水化合物部分直接结合。我们认为n-连接寡糖是维持MCP构象依赖性受体决定因素所必需的。
Membrane cofactor protein (MCP) has been shown to act as a cellular receptor for measles virus. In previous binding studies we demonstrated a direct interaction between the measles virus H protein and MCP. The binding was shown to be independent of the O-glycans but dependent on the N-glycans of MCP. To elucidate the role of N-glycans for the receptor function of MCP, the effect of the glycosylation inhibitors tunicamycin (TM) and 1-deoxymannojirimycin (DMJ) was analyzed. TM which prevents N-glycosylation has been reported to inhibit the expression of functional measles virus receptors. Here we show that MCP lacking all N-glycans was detectable on the surface of Vero cells, although in a reduced amount. Therefore, the lack of receptor activity cannot be explained by intracellular degradation or defective transport. In the presence of DMJ, a mannosidase I inhibitor, MCP is synthesized with N-glycans of the high-mannose type in contrast to the complex oligosaccharides present on MCP of untreated cells. Both MCP with mannose-rich and MCP with complex N-glycans were recognized by measles virus H protein in an in vitro binding assay. They both could also serve as receptors for the infection of cultured Vero cells, arguing against a direct binding of virus to a carbohydrate moiety within the N-glycans of MCP. We propose that N-linked oligosaccharides are required to maintain a conformation-dependent receptor determinant of MCP.