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）旨在了解NMR糖基化对蛋白质的结构，功能和动态的影响。研究单元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），这些途径基于脂质dolichol，并竞争两种甘露糖基供体底物和受体蛋白。从C-甘露糖基化（WP2，与P1 Bakker的合作）的具体作用开始，我们能够在结构上表征和比较一种在一个核磷脂表达系统中产生的C-甘露蛋白和未修饰的蛋白（血栓源1型重复（TSR）1型netrin受体UNC-5）（netrin受体UNK 5）（drosophiala s2细胞）。 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不同PMT的底物特异性和催化机制（WP1，与P7 SINNING和P8 Strahl的合作）。