Comprehensive molecular structure of the eukaryotic ribosome.

Comprehensive molecular structure of the eukaryotic ribosome.
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DOI:
10.1016/j.str.2009.09.015
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发表时间:
2009-12-09
期刊:
Structure (London, England : 1993)
影响因子:
--
通讯作者:
Frank J
Frank J
中科院分区:
其他
文献类型:
--
作者:
Taylor DJ;Devkota B;Huang AD;Topf M;Narayanan E;Sali A;Harvey SC;Frank J

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尽管在过去的十年中出现了大量的细菌70 S核糖体的X射线晶体学模型,但真核生物80 S核糖体的精确原子模型仍然不可用。真核生物核糖体比细菌核糖体具有更多的核糖体蛋白和核糖体RNA,它们参与真核细胞的核糖体外功能。通过将cryo-EM与RNA和蛋白质同源性建模相结合,我们获得了完整的酵母80 S核糖体的原子模型,其中包含所有核糖体RNA扩增片段和所有核糖体蛋白质,可以鉴定出结构同源物。80 S核糖体蛋白的突变或缺失可以废除核糖体的成熟,导致几种人类疾病。我们已经定位了一个这样的蛋白质独特的真核生物,rpS 19e,其突变与钻石-布莱克凡贫血在人类。此外,我们的特点与真核延伸因子2的核糖体的动态柄基地之间的关键和新的相互作用。
Despite the emergence of a large number of X-ray crystallographic models of the bacterial 70S ribosome over the past decade, an accurate atomic model of the eukaryotic 80S ribosome is still not available. Eukaryotic ribosomes possess more ribosomal proteins and ribosomal RNA than bacterial ribosomes, which are implicated in extra-ribosomal functions in the eukaryotic cells. By combining cryo-EM with RNA and protein homology modeling, we obtained an atomic model of the yeast 80S ribosome complete with all ribosomal RNA expansion segments and all ribosomal proteins for which a structural homolog can be identified. Mutation or deletion of 80S ribosomal proteins can abrogate maturation of the ribosome, leading to several human diseases. We have localized one such protein unique to eukaryotes, rpS19e, whose mutations are associated with Diamond-Blackfan anemia in humans. Additionally, we characterize crucial and novel interactions between the dynamic stalk base of the ribosome with eukaryotic elongation factor 2.
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