In Search of Mannolipid Intermediate Flippases

寻找甘露糖脂中间翻转酶

基本信息

批准号：
8548379
负责人：
Charles J Waechter
金额：
$ 27.23万
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/8548379
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年中，该实验室一直在研究原核生物和真核生物的聚糖中间体中多肾上腺素连接的中间体的功能。对细胞外糖的生物合成涉及的拓扑问题的长期兴趣使我们专注于介导这些途径中利用为糖基供体的脂质连接中间体的跨贝贝运动的蛋白质。当前的建议旨在鉴定介导Dimannosyldiacyl -Glycerol和Mannosylphopphopphosphosphordolichol的跨贝碱运动的蛋白质，这是小脂肪菌的Lipomannan组装中的两个甘露脂素中间体。这些研究将为鉴定蛋白质N-糖基化，C-和O-甘露糖基化的相关蛋白质的鉴定提供重要的线索，以及人类中糖基磷脂酰肌醇锚固的生物合成。在这些组装过程中编码膜蛋白的基因的发现对于诊断为糖基化（CDGS）中的潜在遗传误差（CDGS）的潜在遗传误差将是有价值的。