Structural Basis of Tau Interaction With BIN1 and Regulation by Tau Phosphorylation.

ABSTRACT: Bridging integrator-1 (BIN1) gene is associated with an increased risk to develop Alzheimer's disease, a tauopathy characterized by intra-neuronal accumulation of phosphorylated Tau protein as paired helical filaments. Direct interaction of BIN1 and Tau proteins was demonstrated to be mediated through BIN1 SH3 C-terminal domain and Tau (210-240) peptide within Tau proline-rich domain. We previously showed that BIN1 SH3 interaction with Tau is decreased by phosphorylation within Tau proline-rich domain, of at least T231. In addition, the BIN1/Tau interaction is characterized by a dynamic equilibrium between a closed and open conformations of BIN1 isoform 1, involving an intramolecular interaction with its C-terminal BIN1 SH3 domain. However, the role of the BIN1/Tau interaction, and

SUBMITTER: Lasorsa A 

PROVIDER: S-EPMC6246682 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature