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Synergistic Interactions between Repeats in Tau Protein and Aβ Amyloids May Be Responsible for Accelerated Aggregation via Polymorphic States

[Image: see text] Amyloid plaques and neurofibrillary tangles simultaneously accumulate in Alzheimer’s disease (AD). It is known that Aβ and tau exist together in the mitochondria; however, the interactions between Aβ oligomers and tau are controversial. Moreover, it is still unclear which specific...

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Autores principales: Miller, Yifat, Ma, Buyong, Nussinov, Ruth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2011
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109766/
https://www.ncbi.nlm.nih.gov/pubmed/21506544
http://dx.doi.org/10.1021/bi200400u
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author Miller, Yifat
Ma, Buyong
Nussinov, Ruth
author_facet Miller, Yifat
Ma, Buyong
Nussinov, Ruth
author_sort Miller, Yifat
collection PubMed
description [Image: see text] Amyloid plaques and neurofibrillary tangles simultaneously accumulate in Alzheimer’s disease (AD). It is known that Aβ and tau exist together in the mitochondria; however, the interactions between Aβ oligomers and tau are controversial. Moreover, it is still unclear which specific domains in the tau protein can interact with Aβ oligomers and what could be the effect of these interactions. Herein, we examine three different Aβ–tau oligomeric complexes. These complexes present interactions of Aβ with three domains in the tau protein; all contain high β-structure propensity in their R2, R3, and R4 repeats. Our results show that, among these, Aβ oligomers are likely to interact with the R2 domain to form a stable complex with better alignment in the turn region and the β-structure domain. We therefore propose that the R2 domain can interact with soluble Aβ oligomers and consequently promote aggregation. EM and AFM images and dimensions revealed highly polymorphic tau aggregates. We suggest that the polymorphic tau and Aβ–tau aggregates may be largely due to repeat sequences which are prone to variable turn locations along the tau repeats.
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spelling pubmed-31097662011-06-07 Synergistic Interactions between Repeats in Tau Protein and Aβ Amyloids May Be Responsible for Accelerated Aggregation via Polymorphic States Miller, Yifat Ma, Buyong Nussinov, Ruth Biochemistry [Image: see text] Amyloid plaques and neurofibrillary tangles simultaneously accumulate in Alzheimer’s disease (AD). It is known that Aβ and tau exist together in the mitochondria; however, the interactions between Aβ oligomers and tau are controversial. Moreover, it is still unclear which specific domains in the tau protein can interact with Aβ oligomers and what could be the effect of these interactions. Herein, we examine three different Aβ–tau oligomeric complexes. These complexes present interactions of Aβ with three domains in the tau protein; all contain high β-structure propensity in their R2, R3, and R4 repeats. Our results show that, among these, Aβ oligomers are likely to interact with the R2 domain to form a stable complex with better alignment in the turn region and the β-structure domain. We therefore propose that the R2 domain can interact with soluble Aβ oligomers and consequently promote aggregation. EM and AFM images and dimensions revealed highly polymorphic tau aggregates. We suggest that the polymorphic tau and Aβ–tau aggregates may be largely due to repeat sequences which are prone to variable turn locations along the tau repeats. American Chemical Society 2011-04-20 2011-06-14 /pmc/articles/PMC3109766/ /pubmed/21506544 http://dx.doi.org/10.1021/bi200400u Text en Copyright © 2011 American Chemical Society http://pubs.acs.org This is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org.
spellingShingle Miller, Yifat
Ma, Buyong
Nussinov, Ruth
Synergistic Interactions between Repeats in Tau Protein and Aβ Amyloids May Be Responsible for Accelerated Aggregation via Polymorphic States
title Synergistic Interactions between Repeats in Tau Protein and Aβ Amyloids May Be Responsible for Accelerated Aggregation via Polymorphic States
title_full Synergistic Interactions between Repeats in Tau Protein and Aβ Amyloids May Be Responsible for Accelerated Aggregation via Polymorphic States
title_fullStr Synergistic Interactions between Repeats in Tau Protein and Aβ Amyloids May Be Responsible for Accelerated Aggregation via Polymorphic States
title_full_unstemmed Synergistic Interactions between Repeats in Tau Protein and Aβ Amyloids May Be Responsible for Accelerated Aggregation via Polymorphic States
title_short Synergistic Interactions between Repeats in Tau Protein and Aβ Amyloids May Be Responsible for Accelerated Aggregation via Polymorphic States
title_sort synergistic interactions between repeats in tau protein and aβ amyloids may be responsible for accelerated aggregation via polymorphic states
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109766/
https://www.ncbi.nlm.nih.gov/pubmed/21506544
http://dx.doi.org/10.1021/bi200400u
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