Divergent effects of pathological α-synuclein truncations and mutations on phase separation

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Divergent effects of pathological α-synuclein truncations and mutations on phase separation

bioRxiv (preprint) 2024
Soumik Ray, Cecilia Chiodaroli, Azad Farzadfard, Antonin Kunka, Katharina Helga Schott, Sophie Hertel, Kristina Mojtic, Louise Kjær Klausen, Céline Galvagnion, Alexander K. Buell

This study characterized how disease-related C-terminal truncations and familial point mutations affect α-synuclein's liquid–liquid phase separation, finding that truncations dramatically alter condensate thermodynamics and drive rapid sol–gel transitions, while all variants ultimately form amyloid fibrils within their condensates. Flow Induced Dispersion Analysis (FIDA), on a Fida 1 instrument, was used to chart phase diagrams and quantify the dilute-phase concentration of α-synuclein variants via two custom capillary-based assays, TDIPS and Capflex, developed by the authors on the instrument. It is an example of using FIDA to quantitatively characterize biomolecular condensate formation and liquid–liquid phase separation behavior.

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Divergent effects of pathological α-synuclein truncations and mutations on phase separation
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