Tau/A β chimera peptides: Evaluating the dual function of metal coordination and membrane interaction in one sequence.

In this study, we assess the amyloidogenic propensity and membrane-damage effects, either in the presence or in absence of metal ions, of two newly synthesized bifunctional peptides. These were designed to comprise a metal chelating N-terminus region derived from Tau protein namely the Tau9-16 (EVMEDHAG) or Tau26-33 (QGGYTMHQ) sequences, merged with the C-terminal hydrophobic region analogous to the Amyloid beta (Aβ) 16-20 aminoacid sequence KLVFF (KL). Comparative circular dichroism or fluorescence experiments were carried out to look at the peptide conformation, fibril formation and membrane affinity of Tau9-16KL and Tau26-33KL peptides. We found that Tau9-16KL and Tau26-33KL perturb the fibrillogenic process of Aβ1-40. Furthermore Cu(II) and, to a lower extent, Zn(II) induced conformational changes Tau26-33KL both in water and in membrane-mimicking environment. By contrast, due to a different metal coordination mode we observed for Tau9-16KL an unstructured peptide conformation in all the experimental conditions. Unlike aqueous solution, a certain propensity to form amyloid structures at the lipid membrane interface clearly emerged for both the peptides. However, the two peptides exhibit a different capability to elicit membrane damage depending on the presence or absence of metal ions. Tau9-16KL and Tau26-33KL can be used as peptide-based molecular systems able to interfere with the metal dependent Aβ/Tau cross-seeded generation of membrane active amyloid s...
Source: Journal of Inorganic Biochemistry - Category: Biochemistry Authors: Tags: J Inorg Biochem Source Type: research

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