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Quantitative Chemoproteomics Reveals Dopamine’s Protective Modification of Tau

ABSTRACT: Dopamine (DA) is one of the most important neurotransmitters. Oxidation of DA leads to electrophilic quinone intermediates, which can covalently modify nucleophilic residues in proteins, resulting in “dopamination”. Individual dopaminated protein targets have been studied, most of which were functionally damaged by dopamination. Here, we developed a quantitative chemoproteomic strategy to site-specifically measure protein dopamination in mouse brains. More than 6000 dopamination sites were quantified and IC50 values for 64 hyper-sensitive sites were measured. Among them, hyper-sensitive dopamination of two cysteines in microtubule-associated protein Tau were biochemically validated and functionally characterized to prevent Tau’s pathological amyloid fibrillation and promote Tau-mediated assembly of microtubules. Our study not only provided the first global portrait of dopamination with site-specific resolution, but also discovered a protective role of DA in regulating the function of Tau, which may help advance our understanding of the physiological and pathological role of DA in human brain.

ORGANISM(S): Homo Sapiens Mus Musculus

SUBMITTER: Chu Wang

PROVIDER: PXD056638 | iProX | Fri Dec 20 00:00:00 GMT 2024

REPOSITORIES: iProX

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