Wadsworth Center, Empire State Plaza, Albany, NY 12201-0509, USA.
School of Biology and Parker H. Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332-0230, USA.
Structure. 2009 Dec 9;17(12):1591-1604. doi: 10.1016/j.str.2009.09.015.
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 do bacterial ribosomes, which are implicated in extraribosomal 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 interactions between the dynamic stalk base of the ribosome with eukaryotic elongation factor 2.
尽管在过去十年中出现了大量细菌 70S 核糖体的 X 射线晶体结构模型，但真核 80S 核糖体的精确原子模型仍然不存在。真核核糖体比细菌核糖体具有更多的核糖体蛋白和核糖体 RNA，这些核糖体 RNA 参与真核细胞的核糖体外功能。通过将 cryo-EM 与 RNA 和蛋白质同源建模相结合，我们获得了一个完整的酵母 80S 核糖体的原子模型，其中包括所有核糖体 RNA 扩展片段和所有核糖体蛋白，这些核糖体蛋白都可以识别出结构同源物。80S 核糖体蛋白的突变或缺失会导致核糖体成熟，从而导致几种人类疾病。我们已经定位了一种存在于真核生物中的独特蛋白 rpS19e，其突变与人类的 Diamond-Blackfan 贫血有关。此外，我们还描述了核糖体动态茎基部与真核延伸因子 2 之间的关键相互作用。
