In Search of Mannolipid Intermediate Flippases

描述（由申请人提供）：在过去的35年中，本实验室一直在研究聚异戊二醇连接的中间体在原核生物和真核生物中合成聚糖的功能。长期以来对细胞外糖类生物合成中涉及的拓扑问题的兴趣使我们将重点放在介导脂质连接中间体在这些途径中用作糖基供体的跨双层运动的蛋白质上。目前的建议旨在鉴定介导二甘露糖基二酰基甘油和甘露糖基磷酸多醇的跨双分子层运动的蛋白质，这两种甘露糖脂中间体在黄体微球菌的脂甘露聚糖组装中。这些研究将为鉴定参与蛋白质n -糖基化、蛋白质C-和o -甘露糖基化以及人类糖基磷脂酰肌醇锚点生物合成的相关蛋白提供重要线索。发现在这些组装过程中作为翻转酶的膜蛋白编码基因，将对诊断潜在的遗传错误（先天性糖基化疾病（CDGs））有价值。

DESCRIPTION (provided by applicant): During the past 35 years this laboratory has been studying the function of polyisoprenol-linked intermediates in glycan synthesis in prokaryotes and eukaryotes. A long-standing interest in the topological issues involved in the biosynthesis of extracellular saccharides has led us to focus on the proteins that mediate the transbilayer movements of the lipid-linked intermediates utilized as glycosyl donors in these pathways. The current proposal is aimed at identifying the proteins that mediate the transbilayer movement of dimannosyldiacylglycerol and mannosylphosphoryldolichol, two mannolipid intermediates in the assembly of the lipomannan of Micrococcus luteus. These studies will provide important clues to the identification of related proteins functioning in protein N-glycosylation, C- and O-mannosylation of proteins and biosynthesis of glycosylphosphatidylinositol anchors in humans. The discovery of genes encoding membrane proteins functioning as flippases in these assembly processes will be valuable in the diagnosis of potential genetic errors referred to as Congenital Disorders in Glycosylation (CDGs).