Facile Installation of Post-translational Modifications on the Tau Protein via Chemical Mutagenesis
| Autor: | Gonçalo J. L. Bernardes, Ross J Taylor, Philip R. Lindstedt, Michele Vendruscolo |
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| Rok vydání: | 2021 |
| Předmět: |
Physiology
Cognitive Neuroscience Tau protein Mutagenesis (molecular biology technique) tau Proteins Protein aggregation Biochemistry Microtubules Microtubule polymerization 03 medical and health sciences 0302 clinical medicine Microtubule Alzheimer Disease Humans Phosphorylation 030304 developmental biology 0303 health sciences biology Chemistry Cell Biology General Medicine Methylation Mutagenesis biology.protein Biophysics Protein Processing Post-Translational 030217 neurology & neurosurgery Macromolecule |
| Zdroj: | ACS chemical neuroscience. 12(3) |
| ISSN: | 1948-7193 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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