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Content Provider | Directory of Open Access Journals (DOAJ) |
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Author | Bartosz Nizynski Hanna Nieznanska Robert Dec Solomiia Boyko Wojciech Dzwolak Krzysztof Nieznanski |
Abstract | Amyloid aggregates of Tau protein have been implicated in etiology of many neurodegenerative disorders including Alzheimer's disease (AD). When amyloid growth is induced by seeding with preformed fibrils assembled from the same protein, structural characteristics of the seed are usually imprinted in daughter generations of fibrils. This so-called conformational memory effect may be compromised when the seeding involves proteins with non-identical sequences leading to the emergence of distinct structural variants of fibrils (amyloid 'strains'). Here, we investigate cross-seeding of full-length human Tau (FL Tau) with fibrils assembled from K18 and K18ΔK280 fragments of Tau in the presence of poly-L-glutamate (poly-Glu) as an enhancer of Tau aggregation. To study cross-seeding between Tau polypeptides and the role of the conformational memory effect in induction of Tau amyloid polymorphism, kinetic assays, transmission electron microscopy, infrared spectroscopy and limited proteolysis have been employed. The fastest fibrillization was observed for FL Tau monomers seeded with preformed K18 amyloid yielding daughter fibrils with unique trypsin digestion patterns. Morphological features of daughter FL Tau fibrils induced by K18 and K18ΔK280 seeds were reminiscent of the mother fibrils (i.e. straight paired fibrils and paired helical filaments (PHFs), respectively) but disappeared in the following generations which became similar to unpaired FL Tau amyloid fibrils formed de novo. The structural evolution observed in our study was accompanied by disappearance of the unique proteolysis profile originated from K18. Our findings may have implications for understanding molecular mechanisms of the emergence and stability of Tau amyloid strains. |
e-ISSN | 19326203 |
DOI | 10.1371/journal.pone.0201182 |
Journal | PLoS ONE |
Issue Number | 7 |
Volume Number | 13 |
Language | English |
Publisher | Public Library of Science (PLoS) |
Publisher Date | 2018-01-01 |
Publisher Place | United States |
Access Restriction | Open |
Subject Keyword | Medicine Science |
Content Type | Text |
Resource Type | Article |
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