Folding of the Tau Protein on Microtubules
Abstract
Microtubules are regulated by microtubule‐associated proteins. However, little is known about the structure of microtubule‐associated proteins in complex with microtubules. Herein we show that the microtubule‐associated protein Tau, which is intrinsically disordered in solution, locally folds into a stable structure upon binding to microtubules. While Tau is highly flexible in solution and adopts a β‐sheet structure in amyloid fibrils, in complex with microtubules the conserved hexapeptides at the beginning of the Tau repeats two and three convert into a hairpin conformation. Thus, binding to microtubules stabilizes a unique conformation in Tau.
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The conformations induced in Tau upon binding to F-actin and microtubules are very different, because F-actin interaction is connected to helix formation, while short Tau regions fold into a hairpin-like structure in complex with microtubules.
“Notably, the conformations that are induced in Tau upon binding to F-actin and microtubules are very different, because F-actin interaction is connected to helix formation (Fig. 3), while short Tau regions fold into a hairpin-like structure in complex with microtubules46.”
From Multivalent cross-linking of actin filaments and microtubules through the microtubule-associated protein Tau (2017) · cites this paper as [46]
Cites
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Self-citationAlphaFold 2 and NMR Spectroscopy: Partners to Understand Protein Structure, Dynamics and Function
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Tau can switch microtubule network organizations: from random networks to dynamic and stable bundles
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Brotzakis, Z. F., Lindstedt, P. R., Taylor, R. J., Rinauro, D. J., Gallagher, N. C. T., Bernardes, G. J. L., & Vendruscolo, M. (2021) · ACS Central Science · doi:10.1021/acscentsci.1c00585 · Cited by 70 · see citing works
- Authors
- Kadavath, H., Jaremko, M., Jaremko, Ł., Biernat, J., Mandelkow, E., & Zweckstetter, M.
- Affiliations
- German Center for Neurodegenerative Diseases (DE)
- Center of Advanced European Studies and Research (DE)
- Corresponding author
- Zweckstetter, Markus
- Venue
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Published
- 2015-06-19
- Volume
- 54
- Issue
- 35
- Pages
- 10347-10351
- ISSN
- 1433-7851 (ISSN-L)
- 1521-3773
- OpenAlex
- W1830376997
- Cited by
- 153
- References
- 3
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 6 · 2023: 13 · 2022: 12 · 2021: 21 · 2020: 14 · 2019: 16 · 2018: 28 · 2017: 12 · 2016: 9 · 2015: 2
- FWCI
- 11.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Angewandte Chemie International Edition (publishedVersion)
- PubMed (publishedVersion)
- DZNE Pub (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- MPG
- Wellcome Trust
- Foundation for Polish Science START and Ventures Programme
- EU European Regional Development Fund
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- tau protein, microtubules, protein folding, microtubule-associated proteins, intrinsically disordered proteins, hexapeptide, hairpin conformation, beta-sheet, amyloid fibrils
- MeSH terms
- Amyloid, Humans, Microtubules, Magnetic Resonance Spectroscopy, Protein Conformation, tau Proteins, Protein Folding
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