| Abstract |
Misfolding of α-synuclein into amyloid fibrils is the major hallmark of Parkinson’s disease. At the early stages of aggregation, α-synuclein forms multimeric structures known as ‘oligomers’. Some of them serve as nucleation centers and initiate fibrillization. Interaction of α-synuclein oligomers with cellular membranes remains poorly investigated.
Within this project the affinity of α-synuclein oligomers to lipid membranes will be characterized in vitro and will be compared with that of monomeric α-synuclein using fluorescent probes developed in our lab. The charge and fluidity of lipid membranes will be controlled by lipid composition, modulated by means of photoswitchable and caged lipids, and will be monitored using fluorescent probes for membrane rigidity.
References:
1) K. Afitska, A. Fucikova, V. V. Shvadchak & D. A. Yushchenko. Modification of C-Terminus Provides New Insights into the Mechanism of alpha-Synuclein Aggregation. Biophys J, 2017, 113, 2182.
2) V. V. Shvadchak, O. Kucherak, K. Afitska, D. Dziuba & D. A. Yushchenko. Environmentally sensitive probes for monitoring protein-membrane interactions at nanomolar concentrations. BBA-Biomembranes, 2017, 1859, 852-859.
3) J. A. Frank, D. A. Yushchenko, D. J. Hodson, N. Lipstein, J. Nagpal, G. A. Rutter, J. S. Rhee, A. Gottschalk, N. Brose, C. Schultz & D. Trauner. Photoswitchable diacylglycerols enable optical control of protein kinase C. Nature Chemical Biology, 2016, 12, 755.
4) A. Nadler, D. A. Yushchenko, R. Muller, F. Stein, S. H. Feng, C. Mulle, M. Carta & C. Schultz. Exclusive photorelease of signalling lipids at the plasma membrane. Nature Communications, 2015, 6.
|
