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Effect of an amyloidogenic SARS-COV-2 protein fragment on α-synuclein monomers and fibrils

Jana, A. K.; Lander, C. W.; Chesney, A. D.; Hansmann, U. H. E.

2022-02-24 biophysics
10.1101/2022.02.21.481360 bioRxiv
Show abstract

Using molecular dynamic simulations we study whether amyloidogenic regions in viral proteins can initiate and modulate formation of -synuclein aggregates, thought to be the disease-causing agent in Parkinsons Disease. As an example we choose the nine-residue fragment SFYVYSRVK (SK9), located on the C-terminal of the Envelope protein of SARS-COV-2. We probe how the presence of SK9 affects the conformational ensemble of -synuclein monomers and the stability of two resolved fibril polymorphs. We find that the viral protein fragment SK9 may alter -synuclein amyloid formation by shifting the ensemble toward aggregation-prone and preferentially rod-like fibril seeding conformations. However, SK9 has only little effect of the stability of pre-existing or newly-formed fibrils.

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