6qun
Crystal structure of AtGapC1 with the catalytic Cys149 irreversibly oxidized by H2O2 treatment
Structural highlights
FunctionG3PC1_ARATH Key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate. Essential for the maintenance of cellular ATP levels and carbohydrate metabolism. Involved in response to oxidative stress by mediating plant responses to abscisic acid (ABA) and water deficits through the activation of PLDDELTA and production of phosphatidic acid (PA), a multifunctional stress signaling lipid in plants. Required for full fertility. Binds DNA in vitro.[1] [2] Publication Abstract from PubMedProtein 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 Arabidopsis thaliana (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. Glutathionylation primes soluble glyceraldehyde-3-phosphate dehydrogenase for late collapse into insoluble aggregates.,Zaffagnini 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 Proc Natl Acad Sci U S A. 2019 Nov 26. pii: 1914484116. doi:, 10.1073/pnas.1914484116. PMID:31772010[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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