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NMR spectroscopy to study dynamics with applications to immunology and neurodegeneration

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Kinetics of protein dynamics will be discussed on examples of folded and unfolded proteins (1). The role of partially disordered proteins in two fields of research is investigated. One is the adaptor protein SLP65 which interacts with CIN85 (2). 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 perform phase separation which is related to function. We are 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 (3).

(1) C. Smith et al. Proc. Natl. Acad. Sci. USA . 113, 3296-74 (2016); C. Smith et al. Angew. Chem. Int. Ed. 54, 207-10 (2015)

(2) M. Engelke et al. Science signaling: 7 (339) ra79 (2014); J. Kühn et al. Science signaling: 9 (434) ra66 (2016)

(3) 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); J. Wagner et al. Act. Neuropath.130, 619-631 (2015)

This talk is part of the Biophysical Seminars series.

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