論文 - 詳細
| RRC ID | 35488 |
|---|---|
| 著者 | Ling J, Cho C, Guo LT, Aerni HR, Rinehart J, Söll D. |
| タイトル | Protein aggregation caused by aminoglycoside action is prevented by a hydrogen peroxide scavenger. |
| ジャーナル | Mol Cell |
| Abstract |
Protein mistranslation causes growth arrest in bacteria, mitochondrial dysfunction in yeast, and neurodegeneration in mammals. It remains poorly understood how mistranslated proteins cause such cellular defects. Here we demonstrate that streptomycin, a bactericidal aminoglycoside that increases ribosomal mistranslation, induces transient protein aggregation in wild-type Escherichia coli. We further determined the aggregated proteome using label-free quantitative mass spectrometry. To identify genes that reduce cellular mistranslation toxicity, we selected from an overexpression library protein products that increased resistance against streptomycin and kanamycin. The selected proteins were significantly enriched in members of the oxidation-reduction pathway. Overexpressing one of these proteins, alkyl hydroperoxide reductase subunit F (a protein defending bacteria against hydrogen peroxide), but not its inactive mutant suppressed aggregated protein formation upon streptomycin treatment and increased aminoglycoside resistance. This work provides in-depth analyses of an aggregated proteome caused by streptomycin and suggests that cellular defense against hydrogen peroxide lowers the toxicity of mistranslation. |
| 巻・号 | 48(5) |
| ページ | 713-22 |
| 公開日 | 2012-12-14 |
| DOI | 10.1016/j.molcel.2012.10.001 |
| PII | S1097-2765(12)00829-5 |
| PMID | 23122414 |
| PMC | PMC3525788 |
| MeSH | Aminoglycosides / pharmacology* Anti-Bacterial Agents / pharmacology* Drug Resistance, Multiple, Bacterial / genetics Escherichia coli / drug effects* Escherichia coli / genetics Escherichia coli / growth & development Escherichia coli / metabolism Escherichia coli Proteins / biosynthesis* Escherichia coli Proteins / chemistry Escherichia coli Proteins / genetics Free Radical Scavengers / pharmacology* Gene Expression Regulation, Bacterial Hydrogen Peroxide / metabolism* Kanamycin / pharmacology Mass Spectrometry Microbial Viability / drug effects Mutation Oxidative Stress / drug effects* Oxidative Stress / genetics Peroxiredoxins / biosynthesis Peroxiredoxins / genetics Protein Biosynthesis / drug effects* Protein Folding Proteomics / methods Ribosomes / drug effects Ribosomes / metabolism Streptomycin / pharmacology Time Factors |
| IF | 15.584 |
| 引用数 | 54 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| リソース情報 | |
| 原核生物(大腸菌) | ASKA library |