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原核生物和真核生物中聚糖合成中聚异戊二烯醇连接的中间体的功能。一个长期的兴趣，在生物合成的胞外多糖的拓扑问题，使我们专注于蛋白质介导的transbilayer运动的脂质连接的中间体利用糖基供体在这些途径。目前的建议是旨在确定介导的transbilayer运动的二甘露糖二酰甘油和甘露糖磷酰dolichol，两个甘露脂中间体的脂甘露聚糖的微球菌luteus的蛋白质。这些研究将提供重要的线索，在蛋白质N-糖基化，C-和O-甘露糖基化的蛋白质和生物合成的糖基磷脂酰肌醇锚在人类中的功能的相关蛋白质的鉴定。发现编码膜蛋白的基因在这些组装过程中起翻转酶的作用，将在诊断被称为先天性糖基化障碍（CDG）的潜在遗传错误中具有价值。

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).