P. Enke, M. Schleeger, and T. Kiefhaber
Institut für Biochemie und Biotechnologie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Straße 3, 06120 Halle
More than ten diseases are known that are based on the expansion of polyglutamine sequences within the disease-related proteins, which leads to the formation of amyloids. We tested, whether the propensity to form amyloids is due to distinct structural and/or dynamic properties of the monomeric state of polyglutamine (polyQ) chains. Using triplet-triplet energy transfer (TTET) and time-resolved fluorescence resonance energy transfer (trFRET) we were able to characterize the structure (end-to-end distribution) and the intrachain dynamics of monomeric polyQ chains of different length. The results were compared to the properties of the previously characterized model chains poly-(glycine-serine) and poly-serine [1-4] and of fragments from IDPs, which do not form amyloids. The results show that intrachain dynamics in polyQ chains are slower than the dynamics of all other investigated chains and that longer polyQ chains contain a fraction of pre-formed loop structures in the conformational ensemble, which may explain their tendency to form oligomers of β-hairpins.
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