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Subtle change of fibrillation condition leads to substantial alteration of recombinant Tau fibril structure
In vitro assembly of amyloid fibrils that recapitulate those in human brains is very useful for fundamental and applied research on the amyloid formation, pathology, and clinical detection. Recent success in the assembly of Tau fibrils in vitro enables the recapitulation of the paired helical filame...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9732399/ https://www.ncbi.nlm.nih.gov/pubmed/36505939 http://dx.doi.org/10.1016/j.isci.2022.105645 |
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author | Li, Xiang Zhang, Shenqing Liu, Zhengtao Tao, Youqi Xia, Wencheng Sun, Yunpeng Liu, Cong Le, Weidong Sun, Bo Li, Dan |
author_facet | Li, Xiang Zhang, Shenqing Liu, Zhengtao Tao, Youqi Xia, Wencheng Sun, Yunpeng Liu, Cong Le, Weidong Sun, Bo Li, Dan |
author_sort | Li, Xiang |
collection | PubMed |
description | In vitro assembly of amyloid fibrils that recapitulate those in human brains is very useful for fundamental and applied research on the amyloid formation, pathology, and clinical detection. Recent success in the assembly of Tau fibrils in vitro enables the recapitulation of the paired helical filament (PHF) of Tau extracted from brains of patients with Alzheimer’s disease (AD). However, following the protocol, we observed that Tau constructs including 297-391 and a mixture of 266-391 (3R)/297-391, which are expected to predominantly form PHF-like fibrils, form highly heterogeneous fibrils instead. Moreover, the seemingly PHF-like fibril formed by Tau 297-391 exhibits a distinctive atomic structure with a spindle-like fold, that is neither PHF-like or similar to any known Tau fibril structures revealed by cryo-electron microscopy (cryo-EM). Our work highlights the high sensitivity of amyloid fibril formation to subtle conditional changes and suggests high-resolution structural characterization to in vitro assembled fibrils prior to further laboratory use. |
format | Online Article Text |
id | pubmed-9732399 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-97323992022-12-10 Subtle change of fibrillation condition leads to substantial alteration of recombinant Tau fibril structure Li, Xiang Zhang, Shenqing Liu, Zhengtao Tao, Youqi Xia, Wencheng Sun, Yunpeng Liu, Cong Le, Weidong Sun, Bo Li, Dan iScience Article In vitro assembly of amyloid fibrils that recapitulate those in human brains is very useful for fundamental and applied research on the amyloid formation, pathology, and clinical detection. Recent success in the assembly of Tau fibrils in vitro enables the recapitulation of the paired helical filament (PHF) of Tau extracted from brains of patients with Alzheimer’s disease (AD). However, following the protocol, we observed that Tau constructs including 297-391 and a mixture of 266-391 (3R)/297-391, which are expected to predominantly form PHF-like fibrils, form highly heterogeneous fibrils instead. Moreover, the seemingly PHF-like fibril formed by Tau 297-391 exhibits a distinctive atomic structure with a spindle-like fold, that is neither PHF-like or similar to any known Tau fibril structures revealed by cryo-electron microscopy (cryo-EM). Our work highlights the high sensitivity of amyloid fibril formation to subtle conditional changes and suggests high-resolution structural characterization to in vitro assembled fibrils prior to further laboratory use. Elsevier 2022-11-22 /pmc/articles/PMC9732399/ /pubmed/36505939 http://dx.doi.org/10.1016/j.isci.2022.105645 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Li, Xiang Zhang, Shenqing Liu, Zhengtao Tao, Youqi Xia, Wencheng Sun, Yunpeng Liu, Cong Le, Weidong Sun, Bo Li, Dan Subtle change of fibrillation condition leads to substantial alteration of recombinant Tau fibril structure |
title | Subtle change of fibrillation condition leads to substantial alteration of recombinant Tau fibril structure |
title_full | Subtle change of fibrillation condition leads to substantial alteration of recombinant Tau fibril structure |
title_fullStr | Subtle change of fibrillation condition leads to substantial alteration of recombinant Tau fibril structure |
title_full_unstemmed | Subtle change of fibrillation condition leads to substantial alteration of recombinant Tau fibril structure |
title_short | Subtle change of fibrillation condition leads to substantial alteration of recombinant Tau fibril structure |
title_sort | subtle change of fibrillation condition leads to substantial alteration of recombinant tau fibril structure |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9732399/ https://www.ncbi.nlm.nih.gov/pubmed/36505939 http://dx.doi.org/10.1016/j.isci.2022.105645 |
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