ArticlePloS one2012
Fibril-forming motifs are essential and sufficient for the fibrillization of human Tau.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 24 citations in OpenAlex.
- Deciphering Neuroprotective Effect ofCurrent drug targets · 2024Review
- CARs-DB: A Database of Cryptic Amyloidogenic Regions in Intrinsically Disordered Proteins.Frontiers in molecular biosciences · 2022Article
- The Relation between α-Helical Conformation and Amyloidogenicity.Biophysical journal · 2018Article
- Pathological hydrogen peroxide triggers the fibrillization of wild-type SOD1 via sulfenic acid modification of Cys-111.Cell death & disease · 2018Article
- Rosmarinic acid prevents fibrillization and diminishes vibrational modes associated to β sheet in tau protein linked to Alzheimer's disease.Journal of enzyme inhibition and medicinal chemistry · 2017Article
- How does domain replacement affect fibril formation of the rabbit/human prion proteins.PloS one · 2014Article
- The role of crowded physiological environments in prion and prion-like protein aggregation.International journal of molecular sciences · 2013Review
- Protein disulfide isomerase interacts with tau protein and inhibits its fibrillization.PloS one · 2013Article
- MetAmyl: a METa-predictor for AMYLoid proteins.PloS one · 2013Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe misfolding of amyloidogenic proteins including human Tau protein, human prion protein, and human α-synuclein is involved in neurodegenerative diseases such as Alzheimer disease, prion disease, and Parkinson disease. Although a lot of research on such amyloidogenic proteins has been done, we do not know the determinants that drive these proteins to form fibrils and thereby induce neurodegenerative diseases. In this study, we want to know the role of fibril-forming motifs from such amyloidogenic proteins in the fibrillization of human Tau protein. METHODOLOGY/PRINCIPAL
findingsAs evidenced by thioflavin T binding and turbidity assays, transmission electron microscopy, and circular dichroism, fibril-forming motifs are essential and sufficient for the fibrillization of microtubule-associated protein Tau: only when both of its fibril-forming motifs, PHF6 and PHF6*, are deleted can recombinant human Tau fragment Tau(244-372) lose its ability to form fibrils, and the insertion of unrelated fibril-forming motifs from other amyloidogenic proteins, such as human prion protein, yeast prion protein, human α-synuclein, and human amyloid β, into the disabled Tau protein can retrieve its ability to form fibrils. Furthermore, this retrieval is independent of the insertion location on Tau(244-372). CONCLUSIONS/SIGNIFICANCE: We demonstrate for the first time that insertion of fibril-forming motifs can replace PHF6/PHF6* motifs, driving human Tau protein to form fibrils with different morphologies and different kinetic parameters. Our results suggest that fibril-forming motifs play a key role in the fibrillization of human Tau protein and could be the determinants of amyloidogenic proteins tending to misfold, thereby causing the initiation and development of neurodegenerative diseases. Our study also touches on the importance of amyloid "strains": changes to the amyloidgenic driver region results in altered structural morphologies at the macromolecular level.
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