The Role of Dolichol in Protein Glycosylation

描述（由申请人提供）：尚不清楚长萜醇在长萜醇连接的糖基化途径中的作用。 这一重要途径负责内质网（ER）中长轴醇连接十四糖（Dol-PP-（GlcNAc）2 Man 9 Glc 3）的高保真生产。 然后，十四糖通过寡糖基转移酶被整体转移到在粗ER中被翻译的新生蛋白质。 已经提出，多萜醇，一种大的聚类异戊二烯脂质，通过增加膜流动性促进寡糖的产生。 也有人提出，多萜醇起到将发育中的寡糖锚在ER膜上的作用，从而促进膜结合酶之间的转移，所述膜结合酶催化天冬酰胺连接的糖基化酶（ALG）的加成。 这些假设，以及什么样的作用，多萜醇丰富的膜在协会的ALG酶，将进行测试。 这些实验是使用化学和生物学之间的界面上的最先进技术设计的。 最初的工作将是孤立的步骤的途径，并将推进到调查一系列的步骤。 将使用生物物理、化学和生物技术。

DESCRIPTION (provided by applicant): The role of dolichol in the dolichol linked gylcosylation pathway is unknown. This essential pathway is responsible for the high fidelity production of the dolichol-linked tetradecasaccharide, Dol-PP- (GlcNAc)2Man9GIc3, in the endoplasmic reticulum (ER). The tetradecasaccharide is then transferred en block, via the enzyme oligosaccharyltransferase to nascent proteins being translated in the rough ER. It has been proposed that dolichol, a large polyisoprenoid lipid, facilitates the production of the oligosaccaride by increasing membrane fluidity. It has also been proposed that dolichol acts to anchor the developing oligosaccaride to the ER membrane, thereby facilitating transfer between the membrane bound enzymes that catalyze the additions of the saccharides, the asparagine-linked gylcoslyation enzymes (ALG). These hypotheses, as well as what the role of dolichol rich membranes have in the association of the ALG enzymes, will be tested. The experiments are designed using state of the art techniques at the interface between chemistry and biology. Initially work will be on isolated steps of the pathway and will advance to investigating a sequence of steps. Biophysical, chemical and biological techniques will be used.