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Large facilities and the evolving ribosome the cellular machine for genetic-code translation

机译:大型设施和不断发展的核糖体用于遗传密码翻译的细胞机器

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摘要

Well-focused X-ray beams, generated by advanced synchrotron radiation facilities, yielded high-resolution diffraction data from crystals of ribosomes, the cellular nano-machines that translate the genetic code into proteins. These structures revealed the decoding mechanism, localized the mRNA path and the positions of the tRNA molecules in the ribosome and illuminated the interactions of the ribosome with initiation, release and recycling factors. They also showed that the ribosome is a ribozyme whose active site is situated within a universal symmetrical region that is embedded in the otherwise asymmetric ribosome structure. As this highly conserved region provides the machinery required for peptide bond formation and for ribosome polymerase activity, it may be the remnant of the proto-ribosome, a dimeric pre-biotic machine that formed peptide bonds and non-coded polypeptide chains. Synchrotron radiation also enabled the determination of structures of complexes of ribosomes with antibiotics targeting them, which revealed the principles allowing for their clinical use, revealed resistance mechanisms and showed the bases for discriminating pathogens from hosts, hence providing valuable structural information for antibiotics improvement.
机译:由先进的同步加速器辐射设备产生的聚焦良好的X射线束,从核糖体晶体(将遗传密码转化为蛋白质的细胞纳米机器)中产生高分辨率衍射数据。这些结构揭示了核糖体的解码机制,定位了mRNA路径和tRNA分子的位置,并阐明了核糖体与起始,释放和再循环因子的相互作用。他们还表明,核糖体是一种核酶,其活性位点位于一个普遍对称的区域内,该区域嵌入在否则为非对称的核糖体结构中。由于这个高度保守的区域提供了肽键形成和核糖体聚合酶活性所需的机制,因此它可能是原核糖体(形成肽键和未编码多肽链的二聚益生元机器)的残余物。同步辐射还可以确定核糖体与靶向它们的抗生素的复合物的结构,从而揭示了允许其临床应用的原理,揭示了抗药性机制,并为区分病原体和宿主提供了基础,从而为改善抗生素提供了有价值的结构信息。

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