Effects of glycosylation on protein structure, function and dynamics

点击翻译按钮获取中文摘要

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).