Kthiri, F, Le, HT, Gautier, V, Caldas, T, Malki, A, Landoulsi, A, Bohn, C, Bouloc, P and Richarme, G (2010) Protein aggregation in a mutant deficient in yajL, the bacterial homolog of the Parkinsonism-associated protein DJ-1. J. Biol. Chem. 285:10328-36
YajL is the closest prokaryotic homolog of the parkinsonism-associated protein DJ-1 (40% sequence identity and similar three-dimensional structure), a protein of unknown function involved in the cellular response to oxidative stress. We report here that a yajL mutant of Escherichia coli displays an increased sensitivity to oxidative stress. It also exhibits a protein aggregation phenotype in aerobiosis, but not in anaerobiosis or in aerobic cells overexpressing superoxide dismutase, suggesting that protein aggregation depends on the presence of reactive oxygen species produced by respiratory chains. The protein aggregation phenotype of the yajL mutant, which can be rescued by the wild-type yajL gene, but not by the corresponding cysteine 106 mutant allele, is similar to that of multiple mutants deficient in superoxide dismutases and catalases, although intracellular hydrogen peroxide levels were not increased in the yajL mutant, suggesting that protein aggregation in this strain does not result from a hydrogen peroxide detoxification defect. Aggregation-prone proteins included 17 ribosomal proteins, the ATP synthase beta subunit, flagellin, and the outer membrane proteins OmpA and PAL; all of them are part of multiprotein complexes, suggesting that YajL might be involved in optimal expression of these complexes, especially during oxidative stress. YajL stimulated the renaturation of urea-unfolded citrate synthase and the solubilization of the urea-unfolded ribosomal proteins S1 and L3 and was more efficient as a chaperone in its oxidized form than in its reduced form. The mRNA levels of several aggregated proteins of the yajL mutant were severely affected, suggesting that YajL also acts at the level of gene expression. These two functions of YajL might explain the protein aggregation phenotype of the yajL mutant.
Aerobiosis; Anaerobiosis; Catalase/metabolism; Citrate (si)-Synthase/metabolism; Escherichia coli/genetics; Escherichia coli/metabolism; Escherichia coli Proteins/chemistry; Escherichia coli Proteins/genetics; Escherichia coli Proteins/metabolism; Gene Expression Regulation, Bacterial; Humans; Hydrogen Peroxide/metabolism; Intracellular Signaling Peptides and Proteins/chemistry; Mutation/genetics; Oncogene Proteins/chemistry; Oxidative Stress; Protein Conformation; Protein Folding; Reactive Oxygen Species/metabolism; Ribosomal Proteins/metabolism; Superoxide Dismutase/metabolism
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