Effects of glycosylation on protein structure, function and dynamics

糖基化对蛋白质结构、功能和动力学的影响

• 批准号: 445098147
• 负责人: Professor Dr. Harald Schwalbe
• 金额: --
• 依托单位: Institut für Organische Chemie und Chemische Biologie
• 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/445098147?language=en
• 关键词: Effects; glycosylation; protein; structure; function

Our group (P6 Schwalbe) aims to understand the impact of glycosylation on the structure, function and dynamic of proteins by NMR. The focus of the Research Unit are three highly conserved glycosylation pathways (N-glycosylation, C-mannosylation and O-mannosylation) which are based on the lipid dolichol and compete for both mannosyl donor substrates and acceptor proteins. Starting with the specific role of C-mannosylation (WP2, collaboration with P1 Bakker), we were able to structurally characterize and compare a C-mannosylated and unmodified protein (a thrombospondin type 1 repeat (TSR) of the netrin receptor UNC-5) produced in one eukaryotic expression system (Drosophila S2 cells) for the first time. We will extend our structural approach and apply the developed tools to other glycosylation modifications (O-fucosylation and O-mannosylation) to study the impact of the specific modification and to monitor the sugar conformation(s) in solution.Secondly, we are investigating the dynamic interaction of protein O-mannosyltransferases (PMTs) with sugars and O-mannosylated model peptides to get structural insight into substrate specificity and the catalytic mechanism of different PMTs (WP1, collaboration with P7 Sinning and P8 Strahl).

我们的小组（P6 Schwalbe）旨在通过NMR了解糖基化对蛋白质结构，功能和动力学的影响。研究单位的重点是三个高度保守的糖基化途径（N-糖基化，C-甘露糖基化和O-甘露糖基化），它们基于脂质多萜醇，并竞争甘露糖基供体底物和受体蛋白。从C-甘露糖基化的特定作用（WP 2，与P1 Bakker合作）开始，我们能够首次在一个真核表达系统（果蝇S2细胞）中产生的C-甘露糖基化和未修饰的蛋白质（netrin受体的1型血小板反应蛋白重复序列（TSR））的结构特征和比较。我们将扩展我们的结构方法，并将开发的工具应用于其他糖基化修饰（O-岩藻糖基化和O-甘露糖基化）来研究特定修饰的影响并监测溶液中的糖构象。我们正在研究蛋白质O-甘露糖基转移酶（PMT）与糖和O-甘露糖基化模型肽，以获得对底物特异性和不同PMT的催化机制的结构洞察（WP 1，与P7 Sinning和P8 Strahl合作）。