YajL, Prokaryotic Homolog of Parkinsonism-associated Protein DJ-1, Functions as a Covalent Chaperone for Thiol Proteome*

Autor: Gilbert Richarme, Valérie Gautier, Mouadh Mihoub, Sun Shin Cha, Hai Tuong Le, Ahmed Landoulsi, Nadia Messaoudi, Fatoum Kthiri, Abderrahim Malki, Young Jun An
Přispěvatelé: Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biochimie et Biologie Moléculaire - 03/UR/0902, Faculté des Sciences de Bizerte, Faculté des Sciences de Bizerte [Université de Carthage], Université de Carthage - University of Carthage-Université de Carthage - University of Carthage, Marine Biotechnology, Research Center, Korea Ocean Research & Developent Institute, Korea Ocean Research & Developent Institute, PHC-Utique (10G0803), Fondation de la Recherche Medicale, Extreme Genome Research Center program of Ministry of Land, Transport, and Maritime Affairs, Faculté des Sciences de Bizerte
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Ribosomal Proteins
DJ-1
Proteome
Protein Deglycase DJ-1
Protein Disulfide-Isomerases
Protein aggregation
Biochemistry
Aconitase
Protein–protein interaction
03 medical and health sciences
Ribosomal protein
Humans
Parkinson
Disulfides
Sulfhydryl Compounds
Protein disulfide-isomerase
oxidoreductase
Molecular Biology
030304 developmental biology
covalent chaperone
Oncogene Proteins
0303 health sciences
biology
Sequence Homology
Amino Acid
Escherichia coli Proteins
030302 biochemistry & molecular biology
Intracellular Signaling Peptides and Proteins
YajL
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
Cell Biology
nervous system diseases
Oxidative Stress
Protein Synthesis and Degradation
Chaperone (protein)
Mutation
mixed disulfides
biology.protein
Protein folding
Oxidoreductases
Cysteine
Molecular Chaperones
Zdroj: Journal of Biological Chemistry
Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2011, epub ahead of print. ⟨10.1074/jbc.M111.299198⟩
ISSN: 0021-9258
1083-351X
DOI: 10.1074/jbc.M111.299198⟩
Popis: International audience; YajL is the closest Escherichia coli homolog of the Parkinsonism-associated protein DJ-1, a multifunctional oxidative stress response protein whose biochemical function remains unclear. We recently reported the aggregation of proteins in a yajL mutant in an oxidative stress-dependent manner, and that YajL exhibits chaperone activity. Here, we show that YajL displays covalent chaperone and weak protein oxidoreductase activities that are dependent on its exposed cysteine 106. It catalyzes reduced RNase oxidation, scrambled RNase isomerization and insulin reduction, and forms mixed disulfides with many cellular proteins upon oxidative stress. The formation of mixed disulfides was detected by immunoblotting bacterial extracts with anti-YajL antibodies under nonreducing conditions. Disulfides were purified from bacterial extracts on a YajL-affinity column, separated by nonreducing-reducing SDS-PAGE and identified by mass spectrometry. Covalent YajL substrates included ribosomal proteins, aminoacyl-tRNA synthetases, chaperones, catalases, peroxidases, and other proteins containing cysteines essential for catalysis or FeS cluster binding, such as glyceraldehyde-3-phosphate dehydrogenase, aldehyde dehydrogenase, aconitase and FeS cluster-containing subunits of respiratory chains. In addition, we show that DJ-1 also forms mixed disulfides with cytoplasmic proteins upon oxidative stress. These results shed light on the oxydative stress-dependent chaperone function of YajL and identify YajL substrates involved in translation, stress protection, protein solubilization and metabolism. They reveal a crucial role for cysteine 106 and suggest that DJ-1 also functions as a covalent chaperone. These findings are consistent with several defects observed in yajL or DJ-1 mutants, including translational defects, protein aggregation, oxidative stress sensitivity and metabolic deficiencies.
Databáze: OpenAIRE
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