In Search of Mannolipid Intermediate Flippases

描述(申请人提供)：在过去的35年里，本实验室一直在研究原核生物和真核生物中聚异戊二烯连接的中间体在多糖合成中的作用。长期以来，人们对胞外糖类生物合成所涉及的拓扑问题感兴趣，这导致我们将重点放在介导这些途径中用作糖基供体的脂联中间体跨双层运动的蛋白质上。目前的建议旨在确定介导二甘露糖二酰甘油和甘露醇磷酸二醇跨双层运动的蛋白质，这两种甘露糖脂是黄色微球菌脂甘露聚糖组装的中间体。这些研究将为鉴定与蛋白质N-糖基化、蛋白质的C-和O-甘露糖化以及糖基磷脂酰肌醇锚点的生物合成相关的蛋白质提供重要线索。编码膜蛋白的基因在这些组装过程中起着翻转酶的作用，这一发现将对诊断潜在的遗传错误，即先天性糖基化障碍(CDGs)具有重要价值。

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).