Anniversary Lecture

NMR based structural biology in Signalling, Immunity and Cellular and neuronal degeneration and -protection

Prof. Christian Griesinger

The role of partially disordered proteins in two fields of research is investigated. One is the adaptor protein SLP65 which interacts with CIN85 (1). The two proteins are essential for B cell activation. The protein is found to be mainly unstructured and its various segments entertain different functions or interact with membranes, SH3 domains and forming coiled coils. Based on the structures, a molecular lego will be described that reduces the SLP65/CIN85 interaction to its absolutely necessary essentials. The two proteins can form supramolecular structures which might be related to function. Prof. Griesinger´s group is additionally interested in a class of IDPs that are important in neuro- and cellular degeneration, which form oligomers and fibrils. Interference with these aggregates specifically on the oligomer level proves to be a valid concept for treatment of devastating diseases such as Parkinson´s, Alzheimer´s, Creutzfeldt Jacob disease and Type II diabetes mellitus. M. Engelke et al. Science signaling: 7 (339) ra79 (2014), J. Kuhn et al. Science signaling : 9 (434) ra66 (2016) C.W. Bertoncini et al. PNAS 102, 1430-1435 (2005), P. Karpinar et al. EMBO J 28, 3256-3268 {2009), J. Wagner et al. Acta Neuropath. 125, 795-813 (2013), A.A. Deeg, Biochim. Biophys. Act. 1850 (9), 1884-1890 (2015), S. Shi, J. Neuropath. Exp. Neurol. 74(9) 924-933 (2015)