Polyphosphate Initiates Tau Aggregation through Intra- and Intermolecular Scaffolding.

ABSTRACT: The aggregation and deposition of tau is a hallmark of a class of neurodegenerative diseases called tauopathies. Despite intensive study, cellular and molecular factors that trigger tau aggregation are not well understood. Here, we provide evidence for two mechanisms relevant to the initiation of tau aggregation in the presence of cytoplasmic polyphosphates (polyP): changes in the conformational ensemble of monomer tau and noncovalent cross-linking of multiple tau monomers. We identified conformational changes throughout full-length tau, most notably diminishment of long-range interactions between the termini coupled with compaction of the microtubule binding and proline- rich regions. We found that while the proline-rich and microtubule binding regions both contain polyP binding sites, th

SUBMITTER: Wickramasinghe SP 

PROVIDER: S-EPMC6712485 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature