@article {2025,
	title = {Impact of multiple phosphorylations on the tau-R2/tubulin interface},
	journal = {Biochemistry},
	year = {2025},
	abstract = {<p>The phosphorylation of the microtubule-associated tau protein plays a key role in the regulation of its physiological function. In particular, tau hyperphosphorylation affects its binding to the tubulin surface, destabilizing the tau-microtubule interface and leading to the accumulation of fibrillar aggregates in the brain. In this work, we performed classical molecular dynamics simulations for the tau-R2/tubulin assembly with various phosphorylation states of serines 285, 289, and 293. We analyze the resulting trajectories to obtain a detailed view of the protein interface in the complex and the impact of tau phosphorylations on the stability of this assembly and on the mobility of the tubulin disordered C-terminal tails (CTTs). We show how the tubulin CTTs help maintain the tau-R2 fragment on the tubulin surface despite the destabilizing effect induced by phosphorylations. Conversely, tau phosphorylation affects the CTTs\&$\#$39; flexibility and their potential activity as MAP-recruiting hooks. Furthermore, counterion-mediated bridges between the phosphate groups and tubulin glutamates also contribute to the binding of tau-R2 on the MT. Overall, the complex dynamics of this fuzzy phosphorylated assembly shed new light on the importance of the cytoplasmic environment in neurons in the context of Alzheimer\&$\#$39;s disease.</p>
},
	author = {Marien, Jules and Pr{\'e}vost, Chantal and S Sacquin-Mora}
}
