The microtubule binding domain of tau protein
Abstract
Tau protein is a microtubule-associated protein implicated in the spatial and temporal specification of microtubules and has been found in the neurofibrillary tangles of Alzheimer's disease. Determination of tau protein structure has revealed three 18 amino acid repeated sequences hypothesized to be tubulin binding sites. Using tau cDNA clones from human fetal brain, we employed E. coli expression systems to synthesize tau protein and fragments of tau protein in order to identify the microtubule binding site. A fragment containing the three repeated sequences binds microtubules, while the amino-terminal half of the protein does not bind. Fragments containing two or one repeat are also capable of binding, indicating that the basic tubulin interacting unit is one repeat.
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4R tau isoforms show a higher propensity to promote microtubule assembly compared to 3R tau isoforms.
“Since tau binds to microtubules through C-terminal repeats within the microtubule-binding domain, 4R tau isoforms show a higher propensity to promote microtubule assembly compared to 3R tau isoforms [122, 123].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [122]
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- Authors
- Lee, G., Neve, R. L., & Kosik, K. S.
- Affiliations
- Brigham and Women's Hospital (US)
- Boston Children's Hospital (US)
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1989-06
- Volume
- 2
- Issue
- 6
- Pages
- 1615-1624
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1972355725
- Cited by
- 500
- References
- 66
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 13 · 2023: 19 · 2022: 12 · 2021: 19 · 2020: 14 · 2019: 17 · 2018: 13 · 2017: 13 · 2016: 8 · 2015: 12 · 2014: 13 · 2013: 13 · 2012: 13
- FWCI
- 14.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29gm039300-05, 5r01ag006601-13)
- National Institute on Aging (R01 AG06601-01)
- National Institute of General Medical Sciences (R29 GM39300-01)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tau protein, microtubule-binding site, microtubule-associated proteins, tubulin binding, neurofibrillary tangles, Alzheimer's disease, protein structure
- MeSH terms
- Amino Acid Sequence, Base Sequence, Binding Sites, DNA, Humans, Microtubule-Associated Proteins, Microtubules, Molecular Sequence Data, Protein Binding, Recombinant Fusion Proteins, Repetitive Sequences, Nucleic Acid, Sequence Homology, Nucleic Acid, Tubulin, tau Proteins
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