Simulations of an extended Tau/tubulins interface reveal a complex disorder-disorder interplay mediated by the C-terminal tails

Building on a complex between a tubulin protofilament (PF) and a fragment of the Tau protein containing residues 169 to 367, we investigate the dynamics of the disordered elements of the system, namely the tubulin C-terminal tails (CTTs) and the Tau protein, using classical all-atom molecular dynamics simulations. Our results show that CTTs adopt a hook-like dynamic pattern on the bare PF while remaining highly mobile. The binding of Tau on the PF surface alters the dynamics of the α I-CTTs in a sequence-dependent manner. While the repeat domains of Tau are mostly maintained on the PF by weak and strong binding patches with the tubulin cores, the Proline-Rich Region (PRR) relies on the wrapping phenomenon of α I-CTTs to fuzzily stabilize its interaction with the PF. Our study thus provides a deep dive into the dynamic interplay between the Tau protein and the CTTs of microtubules, the latter being characterized extensively using a variety of disorder-adapted metrics.