Mutations in Tau Protein Promote Aggregation by Favoring Extended Conformations

• DOI: 10.1021/jacsau.3c00550
• Publication Date: 2023-12-19T19:00:55Z
• Authors: Kevin Pounot; Clara Piersson; Andrew K. Goring; Frédéric Rosu; Valérie Gabelica; Martin Weik; Songi Han; Yann Fichou
• Keywords: Tau protein

Amyloid aggregation of the intrinsically disordered protein (IDP) tau is involved in several diseases, called tauopathies. Some tauopathies can be inherited due to mutations gene encoding tau, which might favor formation amyloid fibrils. This work aims at deciphering mechanisms through disease-associated single-point promote formation. We combined biochemical and biophysical characterization, notably, small-angle X-ray scattering (SAXS), study six different FTDP-17 derived mutations. found that degrees modulate conformational ensembles, intermolecular interactions, liquid-liquid phase separation propensity. In particular, we a good correlation between lag time mutants their radii gyration. show disfavor intramolecular turn extended conformations aggregation. proposes new connection structural features monomers propensity aggregate, providing novel assay evaluate IDPs.