2012年11月6日 訊 /生物谷BIOON/ --科學(xué)家目前并不確定為何不正確的蛋白質(zhì)形式和聚集成團(tuán)現(xiàn)象是神經(jīng)變性疾病的重要標(biāo)志,，神經(jīng)變性疾病包括肌萎縮側(cè)索硬化(ALS),、阿爾茲海默氏癥和瘋牛病等?？窃?1月1日的國(guó)際雜志Molecular Cell上的研究報(bào)告中,，來(lái)自耶魯大學(xué)的研究者通過(guò)在細(xì)菌中研究疾病的發(fā)病過(guò)程來(lái)揭示不正確形式的蛋白質(zhì)的聚集體的形成過(guò)程。
蛋白質(zhì)是由DNA編碼控制并且在核糖體的裝配下在細(xì)胞中形成,，然而,，有時(shí)候蛋白質(zhì)并不會(huì)被正確地裝配，這些錯(cuò)誤折疊的蛋白質(zhì)就趨向于聚集,。錯(cuò)誤折疊的蛋白質(zhì)的聚集現(xiàn)象就在阿爾茲海默癥患者大腦中表現(xiàn)尤為明顯,。
來(lái)自耶魯?shù)难芯繄F(tuán)隊(duì)揭示了抗生素鏈霉素可以誘發(fā)大腸桿菌蛋白質(zhì)的聚集。使用大規(guī)模的蛋白質(zhì)組學(xué)及遺傳學(xué)篩選技術(shù),，研究者分析了蛋白質(zhì)的聚集現(xiàn)象以及篩選了可以使得大腸桿菌對(duì)抗生素產(chǎn)生耐藥性的細(xì)菌蛋白質(zhì),，最終研究者發(fā)現(xiàn)細(xì)菌中一種特殊的蛋白質(zhì)如何保護(hù)細(xì)菌免于過(guò)氧化氫的壓力，以及這種蛋白質(zhì)如何減弱由于鏈霉素所刺激引發(fā)的蛋白質(zhì)的聚集,。
研究者Soll說(shuō),，蛋白質(zhì)聚集體的特性依然很神秘,，但是我們已經(jīng)初步揭示了其所形成的過(guò)程以及細(xì)胞如何免于蛋白質(zhì)的聚集。
這項(xiàng)研究不僅為揭示細(xì)胞中蛋白質(zhì)聚集體如何形成提供了新的思路,，而且闡明可細(xì)菌如何自我防御來(lái)抵擋毒性危害,，這將幫助科學(xué)家開(kāi)發(fā)出更為有效的抗生素來(lái)抵御細(xì)菌的感染。（生物谷Bioon.com）
編譯自：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
