Repeat motifs of tau bind to the insides of microtubules in the absence of taxol
Open accessAbstract
The tau family of microtubule-associated proteins has a microtubule-binding domain which includes three or four conserved sequence repeats. Pelleting assays show that when tubulin and tau are co- assembled into microtubules, the presence of taxol reduces the amount of tau incorporated. In the absence of taxol, strong binding sites for tau are filled by one repeat motif per tubulin dimer; additional tau molecules bind more weakly. We have labelled a repeat motif with nanogold and used three-dimensional electron cryomicroscopy to compare images of microtubules assembled with labelled or unlabelled tau. With kinesin motor domains bound to the microtubule outer surface to distinguish between alpha- and beta-tubulin, we show that the gold label lies on the inner surface close to the taxol binding site on beta-tubulin. Loops within the repeat motifs of tau have sequence similarity to an extended loop which occupies a site in alpha-tubulin equivalent to the taxol-binding pocket in beta-tubulin. We propose that loops in bound tau stabilize microtubules in a similar way to taxol, although with lower affinity so that assembly is reversible.
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These results are consistent with prior data showing competition between tau and taxol for microtubules.
“These results are consistent with prior data showing competition between tau and taxol for microtubules31.”
From Microtubule lattice spacing governs cohesive envelope formation of tau family proteins (2022) · cites this paper as [31]
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Microtubule lattice spacing governs cohesive envelope formation of tau family proteins
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- Authors
- Kar, S., Fan, J., Smith, M. J., Goedert, M., & Amos, L. A.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Kar, Santwana
- Venue
- The EMBO Journal
- Published
- 2003-01-02
- Volume
- 22
- Issue
- 1
- Pages
- 70-77
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC140040
- OpenAlex
- W1984939118
- Cited by
- 355
- References
- 5
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 11 · 2023: 15 · 2022: 13 · 2021: 12 · 2020: 11 · 2019: 23 · 2018: 28 · 2017: 11 · 2016: 17 · 2015: 15 · 2014: 20 · 2013: 23 · 2012: 18
- FWCI
- 4.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
- Keywords
- tau protein, microtubule-binding domain, repeat motifs, beta-tubulin, alpha-tubulin, microtubule stabilization, microtubule-associated proteins, gold labeling, kinesin motor domain, microtubule assembly
- MeSH terms
- Amino Acid Sequence, Cloning, Molecular, Humans, Image Processing, Computer-Assisted, Kinetics, Microtubules, Models, Molecular, Molecular Sequence Data, Protein Conformation, Recombinant Proteins, Tubulin, tau Proteins, Paclitaxel, Repetitive Sequences, Amino Acid
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