title: New insights into tau-microtubules interaction revealed by isothermal titration calorimetry.
abstract: Microtubule dynamic instability is tightly regulated by coordinated action of stabilizing and destabilizing microtubule associated proteins. Among the stabilizing proteins, tau plays a pivotal role in both physiological and pathological processes. Nevertheless, the detailed mechanism of tau-tubulin interaction is still subject to controversy. In this report, we studied for the first time tau binding to tubulin by a direct thermodynamic method in the absence of any tubulin polymerization cofactors that could influence this process. Isothermal titration calorimetry enabled us to evidence two types of tau-tubulin binding modes: one corresponding to a high affinity binding site with a tau:tubulin stoichiometry of 0.2 and the other one to a low affinity binding site with a stoichiometry of 0.8. The same stoichiometries were obtained at all temperatures tested (10-37°C), indicating that the mechanism of interaction does not depend on the type of tubulin polymer triggered upon tau binding. These findings allowed us to get new insights into the topology of tau on microtubules.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Street 32, 119991 Moscow, Russia.
authors.forename: Philipp O
authors.initials: PO
authors.lastname: Tsvetkov
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Makarov
authors.forename: Soazig
authors.initials: S
authors.lastname: Malesinski
authors.forename: Vincent
authors.initials: V
authors.lastname: Peyrot
authors.forename: Francois
authors.initials: F
authors.lastname: Devred
mesh_terms: D000818:Animals; D002151:Calorimetry / Q000379:methods*; D008870:Microtubules / Q000378:metabolism*; D011485:Protein Binding; D012756:Sheep; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins