Bleichert Franziska, Gagnon Keith T, Brown Bernard A, Maxwell E Stuart, Leschziner Andres E, Unger Vinzenz M, Baserga Susan J
Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
Science. 2009 Sep 11;325(5946):1384-7. doi: 10.1126/science.1176099.
Methylation of ribosomal RNA (rRNA) is required for optimal protein synthesis. Multiple 2'-O-ribose methylations are carried out by box C/D guide ribonucleoproteins [small ribonucleoproteins (sRNPs) and small nucleolar ribonucleoproteins (snoRNPs)], which are conserved from archaea to eukaryotes. Methylation is dictated by base pairing between the specific guide RNA component of the sRNP or snoRNP and the target rRNA. We determined the structure of a reconstituted and catalytically active box C/D sRNP from the archaeon Methanocaldococcus jannaschii by single-particle electron microscopy. We found that archaeal box C/D sRNPs unexpectedly formed a dimeric structure with an alternative organization of their RNA and protein components that challenges the conventional view of their architecture. Mutational analysis demonstrated that this di-sRNP structure was relevant for the enzymatic function of archaeal box C/D sRNPs.
核糖体RNA(rRNA)的甲基化是最佳蛋白质合成所必需的。多个2'-O-核糖甲基化由C/D盒引导核糖核蛋白[小核糖核蛋白(sRNP)和小核仁核糖核蛋白(snoRNP)]进行,这些蛋白从古细菌到真核生物都是保守的。甲基化由sRNP或snoRNP的特定引导RNA成分与靶rRNA之间的碱基配对决定。我们通过单颗粒电子显微镜确定了来自嗜热栖热甲烷球菌的重组且具有催化活性的C/D盒sRNP的结构。我们发现古细菌C/D盒sRNP意外地形成了一种二聚体结构,其RNA和蛋白质成分的组织方式不同,这对其结构的传统观点提出了挑战。突变分析表明,这种二聚体sRNP结构与古细菌C/D盒sRNP的酶功能相关。