It takes tau to tango: Investigating the fuzzy interaction between the R2-repeat domain and tubulin C-terminal tails

Abstract

The microtubule-associated protein (MAP) tau plays a key role in the regulation of microtubule assembly and spatial organisation. Tau hyperphosphorylation affects its binding on the tubulin surface and has been shown to be involved in several pathologies such as Alzheimer disease. As the tau binding site on the microtubule lays close to the disordered and highly flexible tubulin C-terminal tails (CTTs), these are likely to impact the tau-tubulin interaction. Since the disordered tubulin CTTs are missing from the available experimental structures, we used homology modeling to build two complete models of tubulin heterotrimers with different isotypes for the β-tubulin subunit (βI/αI/ βI and βIII/αI/βIII).