FOR 2509: The concert of dolichol-based glycosylation: from molecules to disease models

FOR 2509：基于多萜醇的糖基化的音乐会：从分子到疾病模型

• 批准号: 289991887
• 金额: --
• 依托单位: Zentrum für Molekulare Biologie (ZMBH)
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/289991887?language=en
• 关键词: 2509; concert; dolichol; based; glycosylation

The covalent attachment of sugar units to proteins is a complex posttranslational modification found in all domains of life. N-glycosylation, C-mannosylation and O-mannosylation are prevalent and highly conserved glycosylation pathways, all essential for vertebrate development. The three pathways start in the endoplasmic reticulum, are based on the lipid dolichol and compete for both mannosyl donor substrates and acceptor proteins, which in many cases receive more than one type of glycan. Along these three glycosylation routes, today we know of endoplasmic reticulum associated defects in over 30 genes that cause devastating multisystemic disease manifestations (congenital disorders of glycosylation (CDG-I)), underlining the importance of these processes. So far, the three mentioned glycosylation pathways have been studied independently from each other. However, to understand the complexity of glycosylation disorders, it is imperative to decipher the details of the dolichol-based N-glycosylation, C- and O-mannosylation pathways, as well as the precise conditions for their interconnections. To address these questions on the molecular, cellular and organismal level, we have not only brought together experts in N-glycosylation, C- and O-mannosylation, but also in structural and lipid biochemistry, in proteomics, glycoproteomics, glycomics and lipidomics, as well as in developmental biology. In the frame of the collaborative Research Unit, we can thus make use of the newest methodological developments in the different fields. Our vision is to gain a deeper understanding of dolichol-based glycosylation to facilitate the development of diagnostic tools and new therapeutic approaches.

糖单位与蛋白质的共价附着是一种复杂的翻译后修饰，存在于生命的所有领域。n -糖基化、c -甘露糖基化和o -甘露糖基化是普遍存在且高度保守的糖基化途径，对脊椎动物的发育都至关重要。这三种途径始于内质网，以脂质醇为基础，竞争甘露糖基供体底物和受体蛋白，在许多情况下，受体蛋白接受不止一种类型的聚糖。沿着这三种糖基化途径，今天我们知道超过30种基因的内质网相关缺陷导致毁灭性的多系统疾病表现（先天性糖基化障碍（CDG-I）），强调了这些过程的重要性。到目前为止，上述三种糖基化途径都是相互独立研究的。然而，为了理解糖基化紊乱的复杂性，有必要破译基于醇的n -糖基化、C-和o -甘露糖基化途径的细节，以及它们相互连接的精确条件。为了在分子、细胞和有机体水平上解决这些问题，我们不仅汇集了n -糖基化、C-和o -甘露糖基化方面的专家，而且还汇集了结构和脂质生物化学、蛋白质组学、糖蛋白组学、糖组学和脂质组学以及发育生物学方面的专家。因此，在合作研究单位的框架内，我们可以利用不同领域中最新的方法发展。我们的目标是更深入地了解醇基糖基化，以促进诊断工具和新治疗方法的发展。