In Search of Mannolipid Intermediate Flippases

寻找甘露糖脂中间翻转酶

基本信息

批准号：
8710272
负责人：
Charles J Waechter
金额：
$ 28.22万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-20 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8710272
关键词：
1,2-diacylglycerol Anabolism Benzophenones Biological Assay Cell membrane Cells Chemistry Collection Congenital Disorders Defect Diagnosis Diffuse Diglycerides Dolichol Dolichol Monophosphate Mannose Endoplasmic Reticulum Eukaryota Eukaryotic Cell Face GPI Membrane Anchors Genes Genetic Genomic Library Glycolipids Goals Human In Vitro Insulin Receptor Label Laboratories Lead Link Lipids Mammalian Cell Mannose Mediating Membrane Membrane Glycoproteins Membrane Proteins Metabolic Micrococcus luteus Movement Mutation Oligosaccharides Pathway interactions Play Polysaccharides Process Prokaryotic Cells Protein Biosynthesis Protein C Proteins Proteomics Protoplasts Research Design Rhodopsin Scheme Sodium Channel Suicide Surface Temperature Vesicle Yeasts analog experience extracellular gene discovery glycosylation interest lipomannan man monolayer mutant novel protein function seal temperature sensitive mutant voltage

项目摘要

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).

描述（由申请人提供）：在过去的35年里，该实验室一直在研究聚异戊二烯醇连接的中间体在原核生物和真核生物聚糖合成中的功能。对细胞外糖生物合成所涉及的拓扑问题的长期兴趣使我们关注介导在这些途径中用作糖基供体的脂质连接中间体的跨双层运动的蛋白质。目前的提案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（藤黄微球菌脂甘露聚糖组装中的两种甘露糖脂中间体）跨双层运动的蛋白质。这些研究将为鉴定在蛋白质 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的生物合成中起作用的相关蛋白质提供重要线索。编码在这些组装过程中充当翻转酶的膜蛋白的基因的发现对于诊断被称为先天性糖基化障碍（CDG）的潜在遗传错误具有重要意义。