The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Oxidation of cysteine-322 in the repeat domain of microtubule-associated protein tau controls the in vitro assembly of paired helical filaments.
Abstract
One of the hallmarks of Alzheimer disease is the pathological aggregation of tau protein into paired helical filaments (PHFs) and neurofibrillary tangles. Here we describe the in vitro assembly of recombinant tau protein and constructs derived from it into PHFs. Though whole tau assembled poorly, constructs containing three internal repeats (corresponding to the fetal tau isoform) formed PHFs reproducibly. This ability depended on intermolecular disulfide bridges formed by the single Cys-322. Blocking the SH group, mutating Cys for Ala, or keeping tau in a reducing environment all inhibited assembly. With constructs derived from four-repeat tau (having the additional repeat no. 2 and a second Cys-291), PHF assembly was blocked because Cys-291 and Cys-322 interact within the molecule. PHF assembly was enabled again by mutating Cys-291 for Ala. The synthetic PHFs bound the dye thioflavin S used in Alzheimer disease diagnostics. The data imply that the redox potential in the neuron is crucial for PHF assembly, independently or in addition to pathological phosphorylation reactions.
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“Oxidation of the two cysteine residues has a strong influence on the ability of Tau to form amyloid fibrils46.”
From Liquid–liquid phase separation of the microtubule-binding repeats of the Alzheimer-related protein Tau (2017) · cites this paper as [46]
In the citing paper
“while oxidation promotes fibrillization of 3R-Tau through intermolecular disulfide bond formation”
From Liquid–liquid phase separation of the microtubule-binding repeats of the Alzheimer-related protein Tau (2017) · cites this paper as [46]
In the citing paper
“cysteine oxidation in 4R-Tau delays aggregation, because of the formation of intramolecular S–S bridges between C291 and C32246.”
From Liquid–liquid phase separation of the microtubule-binding repeats of the Alzheimer-related protein Tau (2017) · cites this paper as [46]
In the citing paper
“widely published aggregation data, which consistently reported more efficient fibrillization of K19/3R-Tau when compared to K18/4R-Tau23, 46, 48”
From Liquid–liquid phase separation of the microtubule-binding repeats of the Alzheimer-related protein Tau (2017) · cites this paper as [46]
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Citations
Cites
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Ubiquitin is conjugated with amino-terminally processed tau in paired helical filaments
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Litersky, J. M., & Johnson, G. V. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)45982-0 · Cited by 201
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Cited by
Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders
Ballatore, C., Lee, V. M.-Y., & Trojanowski, J. Q. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2194 · Cited by 2,174
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Self-citationTau pathology in Alzheimer disease and other tauopathies
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Metadata
- Authors
- Schweers, O., Mandelkow, E. M., Biernat, J., & Mandelkow, E.
- Affiliations
- Max-Planck Unit for Structural Molecular Biology, c/o Deutsches Elektronen Synchroton, Hamburg, Germany.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1995-08-29
- Volume
- 92
- Issue
- 18
- Pages
- 8463-8467
- ISSN
- 0027-8424
- 1091-6490
- Cited by
- 334
- References
- 4
- Language
- en
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- Schweers, O., Mandelkow, E. M., Biernat, J., & Mandelkow, E. (1995). Oxidation of cysteine-322 in the repeat domain of microtubule-associated protein tau controls the in vitro assembly of paired helical filaments. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.92.18.8463
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
