Tau stabilizes microtubules by binding at the interface between tubulin heterodimers
Tau stabilizes microtubules by binding at the interface between tubulin heterodimers
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DOI：
10.1073/pnas.1504081112
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发表时间：
2015-06-16
影响因子：
11.1
通讯作者：
Zweckstetter, Markus
中科院分区：
文献类型：
--
作者：
Kadavath, Harindranath;Hofele, Romina V.;Zweckstetter, Markus
微管的结构、动力学行为和空间组织由微管相关蛋白调节。一种重要的微管相关蛋白是Tau蛋白，因为它的微管相互作用在阿尔茨海默病和几种其他神经退行性疾病的过程中受损。在这里，我们表明，Tau结合微管通过使用小群体的进化保守残基。结合位点由Tau的病理性聚集所必需的残基形成，表明生理相互作用和致病性错误折叠之间的竞争。当Tau与微管结合时，微管结合位点之间的Tau残基保持柔性，这与Tau-微管相互作用的高度动态性质一致。通过结合在微管蛋白异源二聚体之间的界面，Tau使用微管聚合的保守机制，从而调节轴突稳定性和细胞形态。
The structure, dynamic behavior, and spatial organization of microtubules are regulated by microtubule-associated proteins. An important microtubule-associated protein is the protein Tau, because its microtubule interaction is impaired in the course of Alzheimer's disease and several other neurodegenerative diseases. Here, we show that Tau binds to microtubules by using small groups of evolutionary conserved residues. The binding sites are formed by residues that are essential for the pathological aggregation of Tau, suggesting competition between physiological interaction and pathogenic misfolding. Tau residues in between the microtubule-binding sites remain flexible when Tau is bound to microtubules in agreement with a highly dynamic nature of the Tau-microtubule interaction. By binding at the interface between tubulin heterodimers, Tau uses a conserved mechanism of microtubule polymerization and, thus, regulation of axonal stability and cell morphology.