Signature of an aggregation-prone conformation of tau.

ABSTRACT: The self-assembly of the microtubule associated tau protein into fibrillar cell inclusions is linked to a number of devastating neurodegenerative disorders collectively known as tauopathies. The mechanism by which tau self-assembles into pathological entities is a matter of much debate, largely due to the lack of direct experimental insights into the earliest stages of aggregation. We present pulsed double electron-electron resonance measurements of two key fibril-forming regions of tau, PHF6 and PHF6*, in transient as aggregation happens. By monitoring the end-to-end distance distribution of these segments as a function of aggregation time, we show that the PHF6^(*) regions dramatically extend to distances commensurate with extended β-strand structures within the earliest stages

SUBMITTER: Eschmann NA 

PROVIDER: S-EPMC5356194 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature