Molecular recognition of pathological tau fibril conformations

Abstract

Tau is an intrinsically disordered protein that binds microtubules in healthy neurons but forms pathological aggregates (fibrils) that drive neurodegenerative diseases known as tauopathies. Structures from patient brain tissues revealed that fibrils adopt unique tauopathy-dependent conformations that differ from those of heparin-induced recombinant tau fibrils in vitro. An understanding of the cellular factors driving conformation-specific fibrillization is hampered by a lack of tools for determining fibril conformation and an incomplete understanding of molecular crosstalk with tau posttranslational modifications.