Glutathionylation primes soluble glyceraldehyde-3-phosphate dehydrogenase for late collapse into insoluble aggregates.

TitleGlutathionylation primes soluble glyceraldehyde-3-phosphate dehydrogenase for late collapse into insoluble aggregates.
Publication TypeJournal Article
Year of Publication2019
AuthorsZaffagnini M, Marchand CH, Malferrari M, Murail S, Bonacchi S, Genovese D, Montalti M, Venturoli G, Falini G, Baaden M, Lemaire SD, Fermani S, Trost P
JournalProc Natl Acad Sci U S A
Volume116
Issue51
Pagination26057-26065
Date Published2019 12 17
ISSN1091-6490
Abstract

Protein aggregation is a complex physiological process, primarily determined by stress-related factors revealing the hidden aggregation propensity of proteins that otherwise are fully soluble. Here we report a mechanism by which glycolytic glyceraldehyde-3-phosphate dehydrogenase of (AtGAPC1) is primed to form insoluble aggregates by the glutathionylation of its catalytic cysteine (Cys149). Following a lag phase, glutathionylated AtGAPC1 initiates a self-aggregation process resulting in the formation of branched chains of globular particles made of partially misfolded and totally inactive proteins. GSH molecules within AtGAPC1 active sites are suggested to provide the initial destabilizing signal. The following removal of glutathione by the formation of an intramolecular disulfide bond between Cys149 and Cys153 reinforces the aggregation process. Physiological reductases, thioredoxins and glutaredoxins, could not dissolve AtGAPC1 aggregates but could efficiently contrast their growth. Besides acting as a protective mechanism against overoxidation, S-glutathionylation of AtGAPC1 triggers an unexpected aggregation pathway with completely different and still unexplored physiological implications.

DOI10.1073/pnas.1914484116
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
Citation Key2019|2076
PubMed ID31772010
PubMed Central IDPMC6926014