The structure of microtubule-bound tau

微管结合tau蛋白的结构

• 批准号: 221226297
• 负责人: Professor Dr. Markus Zweckstetter
• 金额: --
• 依托单位: Forschungsgruppe Translationale strukturelle Biologie der Demenz
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/221226297?language=en
• 关键词: structure; microtubule; bound; tau

The tau protein is a neuronal microtubule-associated protein which stabilizes microtubules and regulates the transport of cargo along microtubules. Although intense research has revealed much about the function of the protein tau and its involvement in Alzheimer's disease during the past years, it still remains unclear how tau binds to microtubules. Here I propose to characterize the structural properties of tau bound to microtubules using NMR spectroscopy. Information about the precise nature of the interactions between tau and microtubules is of central importance as altered tau-microtubule interactions change the balance in the fraction of tau bound to microtubules versus soluble tau and lead to depolymerisation of microtubules and formation tau tangles a behaviour that has been implicated in a large number of neurodegenerative diseases.

tau蛋白是一种神经元微管相关蛋白，其稳定微管并调节货物沿着微管的运输。尽管在过去的几年里，深入的研究已经揭示了tau蛋白的功能及其与阿尔茨海默病的关系，但仍不清楚tau蛋白如何与微管结合。在这里，我建议使用NMR光谱表征结合到微管的tau蛋白的结构特性。关于tau和微管之间相互作用的精确性质的信息是至关重要的，因为改变的tau-微管相互作用改变了结合到微管的tau与可溶性tau的比例的平衡，并导致微管的解聚和形成tau缠结，这是一种与大量神经退行性疾病有关的行为。

项目成果

Tau stabilizes microtubules by binding at the interface between tubulin heterodimers

• DOI: 10.1073/pnas.1504081112
• 发表时间: 2015-06-16
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Kadavath, Harindranath;Hofele, Romina V.;Zweckstetter, Markus
• 通讯作者: Zweckstetter, Markus