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 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.
UMR CNRS 6032, Faculté de Pharmacie, 27 Boulevard Jean Moulin, 13385 Cedex 5, Marseille, France.
François
F
Devred
Soazig
S
Douillard
Claudette
C
Briand
Vincent
V
Peyrot
D000818:Animals; D001665:Binding Sites; D007700:Kinetics; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism; D010766:Phosphorylation; D012091:Repetitive Sequences, Nucleic Acid; D012694:Serine / Q000378:metabolism*; D013552:Swine; D013816:Thermodynamics; D014404:Tubulin / Q000378:metabolism* / Q000648:ultrastructure; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
D010455:Peptides; D014404:Tubulin; D016875:tau Proteins; D012694:Serine; D017239:Paclitaxel