# Evaluating the Impact of Phosphorylation on the Dynamics of the Tau Protein Proline-Rich Region

## TL;DR

This study explores how phosphorylation affects the structure of a key region in the TAU protein linked to Alzheimer's disease.

## Contribution

The novel contribution is using computational methods to compare conformational changes between phosphorylated and non-phosphorylated TAU fragments.

## Key findings

- The non-phosphorylated TAU fragment prefers compact conformations.
- Phosphorylation does not significantly alter compactness under experimental restraints.

## Abstract

The
proline-rich region of the tubulin-associated unit
(TAU) protein
is of substantial interest in understanding neurodegenerative diseases
due to its interaction with bridging integrator 1 (BIN1). The associated
gene BIN1 is substantially associated with the development
of Alzheimer’s disease. Previous studies have underlined the
importance of the conformation of the proline-rich region of TAU and
the effect of its phosphorylation. In this study, we investigate the
change in compactness between a four times phosphorylated TAU fragment
(210–240) compared to the unphosphorylated (non-P) form using
computational means. We apply our Ensemble Reconstruction from Fragments
(ERF) approach to create two unbiased conformational ensembles from
which a reweighted ensemble is derived that agrees with observables
from nuclear magnetic resonance experiments. The resulting shift of
the radius of gyration indicates a preference for relatively compact
conformations for the non-P form, while the restraints derived from
the experimental data do not substantially influence the compactness
of the phosphorylated peptide.