CUED Publications database

Facile Installation of Post-translational Modifications on the Tau Protein via Chemical Mutagenesis.

Lindstedt, PR and Taylor, RJ and Bernardes, GJL and Vendruscolo, M (2020) Facile Installation of Post-translational Modifications on the Tau Protein via Chemical Mutagenesis. ACS Chem Neurosci, 12. pp. 557-561.

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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.

Item Type: Article
Uncontrolled Keywords: Alzheimer’s disease Post-translational chemical mutagenesis dehydroalanine methylation phosphorylation protein aggregation
Subjects: UNSPECIFIED
Divisions: UNSPECIFIED
Depositing User: Cron Job
Date Deposited: 20 Jan 2021 20:09
Last Modified: 13 Apr 2021 10:17
DOI: 10.1021/acschemneuro.0c00761