Facile Installation of Post-translational Modifications on the Tau Protein via Chemical Mutagenesis.
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Publication Date
2021-02-03Journal Title
ACS Chem Neurosci
ISSN
1948-7193
Publisher
American Chemical Society (ACS)
Volume
12
Issue
3
Pages
557-561
Language
eng
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Lindstedt, P. R., Taylor, R. J., Lopes Bernardes, G., & Vendruscolo, M. (2021). Facile Installation of Post-translational Modifications on the Tau Protein via Chemical Mutagenesis.. ACS Chem Neurosci, 12 (3), 557-561. https://doi.org/10.1021/acschemneuro.0c00761
Abstract
Post-translational modifications of proteins are ubiquitous in living organisms, as they enable an accurate control of the interactions of these macromolecules. For mechanistic studies, it would be highly advantageous to be able to produce in vitro post-translationally modified proteins with site-specificity. Here, we demonstrate one facile way to achieve this goal through the use of post-translational chemical mutagenesis. We illustrate this approach by performing site-specific phosphorylation and methylation of tau, a protein that stabilizes microtubules and whose aggregation is closely linked with Alzheimer's disease. We then verify the effects of the post-translational modifications on the ability of tau to control microtubule polymerization, revealing in particular an unexpected role for phosphorylation at S199, which is outside the microtubule-binding region of tau. These results show how the chemical mutagenesis approach that we present enables the systematic analysis of site-specific post-translational modifications of a key protein involved in the pathogenesis of Alzheimer's disease.
Keywords
Microtubules, Humans, Alzheimer Disease, tau Proteins, Protein Processing, Post-Translational, Mutagenesis, Phosphorylation
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/M011194/1)
Identifiers
External DOI: https://doi.org/10.1021/acschemneuro.0c00761
This record's URL: https://www.repository.cam.ac.uk/handle/1810/319226
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