Function of the yeast oligosaccharyltransferase complex

描述(由申请人提供)： 膜蛋白和分泌蛋白的N-糖基化是所有真核生物中发生的一个重要的共翻译事件。N-糖基化可能会影响蛋白质的构象和在蛋白质分选和靶向中的功能。最近的证据表明，N-糖基化有助于蛋白质在内质网合成过程中的折叠过程，并可能参与正确的二硫键的形成。一种膜酶，寡糖转移酶(OT)，催化粗面内质网管腔内新生多肽的N-糖基化。我们建议鉴定OT复合体的亚基，识别并结合活性寡糖供体GIc3Man9GIcNAc2-PP-dolicol，并表征与OT功能相关的结合。一种新型的光亲和探针将被用来鉴定OT复合体的底物结合部位。了解OT的底物结合部位将有助于我们更好地了解这种ER膜酶的功能。对这一关键酶的表征将使我们更好地了解糖蛋白的生物合成，并帮助我们设计调节这一过程的药物和治疗方法。未来的医学分支包括细胞生长调控的目标，包括抗癌药物和抗生素的设计。

DESCRIPTION (provided by applicant): The N-glycosylation of membrane and secretory proteins is an essential co-translational event that occurs in all eukaryotes. N-glycosylation may affect protein conformation and function in protein sorting and targeting. Recent evidence suggests that N-glycosylation contributes to the folding process of proteins during synthesis within the ER and may participate in the formation of correct disulfide bridges. A membrane enzyme, oligosaccharyl transferase (OT), catalyzes the N-glycosylation of nascent polypeptides in the lumen of the rough ER. We propose to identify the subunit of the OT complex that recognizes and binds the active oligosaccharyl donor, GIc3Man9GIcNAc2-PP-dolichol and characterize the binding as it relates to OT function. A novel photoaffinity probe will be utilized to identify the substrate binding site of the OT complex. Knowledge of the substrate binding sites of OT will allow us to better understand the function of this ER membrane enzyme. Characterization of this key enzyme will allow us to better understand glycoprotein biosynthesis and help us design drugs and treatments to regulate this process. Future medical ramifications include targets for cell growth regulation, including the design of anticancer drugs and antibiotics.