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First tau repeat domain binding to growing and taxol‐stabilized microtubules, and serine 262 residue phosphorylation
Author(s) -
Devred François,
Douillard Soazig,
Briand Claudette,
Peyrot Vincent
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)02999-x
Subject(s) - microtubule , tubulin , phosphorylation , chemistry , biophysics , peptide , tau protein , serine , in vitro , binding site , residue (chemistry) , microbiology and biotechnology , biochemistry , biology , alzheimer's disease , medicine , disease , pathology
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 R1 (QTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQI), reproducing the first tau microtubule binding motif. We thermodynamically characterized the molecular mechanism of tubulin assembly with R1 in vitro, and measured, for the first time, the binding parameters of R1 on both growing and taxol‐stabilized microtubules. In addition, we obtained similar binding parameters with R1 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.