2012年11月6日 讯 /生物谷BIOON/ --科学家目前并不确定为何不正确的蛋白质形式和聚集成团现象是神经变性疾病的重要标志，神经变性疾病包括肌萎缩侧索硬化(ALS)、阿尔兹海默氏症和疯牛病等。刊登在11月1日的国际杂志Molecular Cell上的研究报告中，来自耶鲁大学的研究者通过在细菌中研究疾病的发病过程来揭示不正确形式的蛋白质的聚集体的形成过程。
蛋白质是由DNA编码控制并且在核糖体的装配下在细胞中形成，然而，有时候蛋白质并不会被正确地装配，这些错误折叠的蛋白质就趋向于聚集。错误折叠的蛋白质的聚集现象就在阿尔兹海默症患者大脑中表现尤为明显。
来自耶鲁的研究团队揭示了抗生素链霉素可以诱发大肠杆菌蛋白质的聚集。使用大规模的蛋白质组学及遗传学筛选技术，研究者分析了蛋白质的聚集现象以及筛选了可以使得大肠杆菌对抗生素产生耐药性的细菌蛋白质，最终研究者发现细菌中一种特殊的蛋白质如何保护细菌免于过氧化氢的压力，以及这种蛋白质如何减弱由于链霉素所刺激引发的蛋白质的聚集。
研究者Soll说，蛋白质聚集体的特性依然很神秘，但是我们已经初步揭示了其所形成的过程以及细胞如何免于蛋白质的聚集。
这项研究不仅为揭示细胞中蛋白质聚集体如何形成提供了新的思路，而且阐明可细菌如何自我防御来抵挡毒性危害，这将帮助科学家开发出更为有效的抗生素来抵御细菌的感染。（生物谷Bioon.com）
编译自：Bacteria yield clues about why proteins go bad in ALS and Alzheimer's
doi:10.1016/j.molcel.2012.10.001
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Protein Aggregation Caused by Aminoglycoside Action Is Prevented by a Hydrogen Peroxide Scavenger
Jiqiang Ling, Chris Cho, Li-Tao Guo, Hans R. Aerni, Jesse Rinehart, Dieter Söll
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
