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

Post-translational modifications of proteins are ubiquitous in living organisms, as they enable an accurate control the interactions these macromolecules. For mechanistic studies, it would be highly advantageous to able produce vitro post-translationally modified with site-specificity. Here, we demonstrate one facile way achieve this goal through use post-translational chemical mutagenesis. We illustrate approach by performing site-specific phosphorylation and methylation tau, a protein that stabilizes microtubules whose aggregation is closely linked Alzheimer’s disease. then verify effects on ability tau microtubule polymerization, revealing particular unexpected role for at S199, which outside microtubule-binding region tau. These results show how mutagenesis present enables systematic analysis key involved pathogenesis