首先是tau重复结构域与生长中的微管和紫杉醇稳定的微管结合，以及丝氨酸262残基的磷酸化。

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

作者信息

Devred François, Douillard Soazig, Briand Claudette, Peyrot Vincent

机构信息

UMR CNRS 6032, Faculté de Pharmacie, 27 Boulevard Jean Moulin, 13385 Cedex 5, Marseille, France.

出版信息

FEBS Lett. 2002 Jul 17;523(1-3):247-51. doi: 10.1016/s0014-5793(02)02999-x.

DOI:10.1016/s0014-5793(02)02999-x

PMID:12123840

Abstract

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.

摘要

tau蛋白磷酸化在微管稳定和阿尔茨海默病中起着关键作用。为了表征tau蛋白与微管结合的分子机制，我们合成了肽R1（QTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQI），它重现了tau蛋白的首个微管结合基序。我们在体外对R1与微管蛋白组装的分子机制进行了热力学表征，并首次测量了R1在生长中的微管和紫杉醇稳定的微管上的结合参数。此外，我们对Ser262位点磷酸化的R1也获得了类似的结合参数。这些数据表明，Ser262位点磷酸化对tau蛋白与微管结合以及微管蛋白组装的影响是由于tau蛋白分子内的大规模重排所致。