6QUQ

Crystal structure of glutathionylated glycolytic glyceraldehyde-3- phosphate dehydrogenase from Arabidopsis thaliana (AtGAPC1)

6QUQ の概要

• エントリーDOI: 10.2210/pdb6quq/pdb
• 関連するPDBエントリー: 4Z0H
• 分子名称: Glyceraldehyde-3-phosphate dehydrogenase GAPC1, cytosolic, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: rossman fold, oxidoreductase activity, nad, cytosolic, glutathione, oxidoreductase
• 由来する生物種: Arabidopsis thaliana (Mouse-ear cress)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 75649.35

構造登録者

Fermani, S.,Zaffagnini, M.,Falini, G.,Trost, P. (登録日: 2019-02-28, 公開日: 2019-12-04, 最終更新日: 2024-01-24)

主引用文献

Zaffagnini, M.,Marchand, C.H.,Malferrari, M.,Murail, S.,Bonacchi, S.,Genovese, D.,Montalti, M.,Venturoli, G.,Falini, G.,Baaden, M.,Lemaire, S.D.,Fermani, S.,Trost, P.
Glutathionylation primes soluble glyceraldehyde-3-phosphate dehydrogenase for late collapse into insoluble aggregates.
Proc.Natl.Acad.Sci.USA, 116:26057-26065, 2019

PubMed 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.

PubMed: 31772010
DOI: 10.1073/pnas.1914484116

実験手法

X-RAY DIFFRACTION (2.993 Å)