Project Details
Projekt
Multiscale simulations and NMR spectroscopy of ubiquitin chains: linkage chemistry and chain behavior (B09*)
Subject Area
Biophysics
Term
from 2016 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 189682160
We aim at unravelling the intrinsic properties of differently linked ubiquitin chains which dictate the fate of ubiquitylated proteins. Structural and dynamic information on an atomistic level will be obtained by the synergistic application of high-resolution NMR spectroscopy and multiscale molecular dynamics simulation. One strength of the proposed work lies in the experimental accessibility of ubiquitin tri- and tetramers with highly specific isotopic labeling of individual ubiquitin moieties in the chain. Thus we will be able to investigate structural and dynamic properties, solvent accessibility, ligand binding and binding affinities specifically for each ubiquitin unit. Molecular interpretation of the NMR data and mechanistic insight into coupling of conformational behavior and interactions with binding partners will be provided by accompanying multiscale simulations. Our combined NMR spectroscopic / multiscale-simulation approach gives us a powerful new tool to investigate the existing variety of ubiquitylation and to obtain a better understanding of ubiquitylation as one fundamental proteostatic process.
DFG Programme
Collaborative Research Centres
Applicant Institution
Universität Konstanz
Project Heads
Professor Dr. Michael Kovermann; Professorin Dr. Christine Peter
