Michael Kovermann / Christine Peter
Multiscale simulations and NMR spectroscopy of ubiquitin chains: linkage chemistry and chain behavior
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 all linked ubiquitin dimers occuring in nature (via project B03). This allows to establish a molecular level interpretation of the influence of linkage type on the chain properties of poly-ubiquitin and its recognition by other proteins. The development of the combined NMR spectroscopic / multiscale-simulation approach will give 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.