First tau repeat domain binding to growing and taxol- stabilized microtubules, and serine 262 residue phosphorylation

Tau phosphorylation plays a crucial role in microtubule stabilization and in Alzheimer's disease. To characterize the molecular mechanisms of tau binding on microtubules, we synthesized the peptide RI (QTAPVPMPDLKNVKSKIGST-ENLKHQPGGGKVQI), reproducing the first tau microtubule binding motif. We thermodynamically characterized the molecular mechanism of tubulin assembly with RI in vitro, and measured, for the first time, the binding parameters of RI on both growing and taxol-stabilized microtubules. In addition, we obtained similar binding parameters with RI phosphorylated on Ser262. These data suggest that the consequences of Ser262 phosphorylation on tau binding to microtubules and on tubulin assembly are due to large intramolecular rearrangements of the tau protein. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.