Remodeling of the conformational ensemble of the repeat domain of tau by an aggregation enhancer

Misfolding of the microtubule‐associated protein Tau is a hallmark of Alzheimer disease and several other neurodegenerative disorders. Because of the dynamic nature of the Tau protein, little is known about the changes in Tau structure that occur during misfolding. Here we studied the structural con...

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محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Akoury, Elias (author)
مؤلفون آخرون: Mukrasch, Marco D. (author), Biernat, Jacek (author), Tepper, Katharina (author), Ozenne, Valery (author), Mandelkow, Eckhard (author), Blackedge, Martin (author), Zweckstetter, Markus (author)
التنسيق: article
منشور في: 2016
الوصول للمادة أونلاين:http://hdl.handle.net/10725/10254
https://doi.org/10.1002/pro.2911
http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php
https://onlinelibrary.wiley.com/doi/full/10.1002/pro.2911
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الوصف
الملخص:Misfolding of the microtubule‐associated protein Tau is a hallmark of Alzheimer disease and several other neurodegenerative disorders. Because of the dynamic nature of the Tau protein, little is known about the changes in Tau structure that occur during misfolding. Here we studied the structural consequences upon binding of the repeat domain of Tau, which plays a key role in pathogenic aggregation, to an aggregation enhancer. By combining NMR experiments with molecular simulations we show that binding of the aggregation enhancer polyglutamic acid remodels the conformational ensemble of Tau. Our study thus provides insight into an early event during misfolding of Tau.