Törö I, Thore S, Mayer C, Basquin J, Séraphin B, Suck D
European Molecular Biology Laboratory, Meyerhofstrasse 1, Postfach 102209, 69012 Heidelberg, Germany.
EMBO J. 2001 May 1;20(9):2293-303. doi: 10.1093/emboj/20.9.2293.
Eukaryotic Sm and Sm-like proteins associate with RNA to form the core domain of ribonucleoprotein particles involved in pre-mRNA splicing and other processes. Recently, putative Sm proteins of unknown function have been identified in Archaea. We show by immunoprecipitation experiments that the two Sm proteins present in Archaeoglobus fulgidus (AF-Sm1 and AF-Sm2) associate with RNase P RNA in vivo, suggesting a role in tRNA processing. The AF-Sm1 protein also interacts specifically with oligouridylate in vitro. We have solved the crystal structures of this protein and a complex with RNA. AF-Sm1 forms a seven-membered ring, with the RNA interacting inside the central cavity on one face of the doughnut-shaped complex. The bases are bound via stacking and specific hydrogen bonding contacts in pockets lined by residues highly conserved in archaeal and eukaryotic Sm proteins, while the phosphates remain solvent accessible. A comparison with the structures of human Sm protein dimers reveals closely related monomer folds and intersubunit contacts, indicating that the architecture of the Sm core domain and RNA binding have been conserved during evolution.
真核生物的Sm蛋白和Sm样蛋白与RNA结合,形成参与前体mRNA剪接及其他过程的核糖核蛋白颗粒的核心结构域。最近,在古细菌中发现了功能未知的假定Sm蛋白。我们通过免疫沉淀实验表明,嗜热栖热菌中存在的两种Sm蛋白(AF-Sm1和AF-Sm2)在体内与RNase P RNA结合,提示其在tRNA加工中发挥作用。AF-Sm1蛋白在体外也能与寡聚尿苷酸特异性相互作用。我们解析了该蛋白及其与RNA复合物的晶体结构。AF-Sm1形成一个七聚体环,RNA在甜甜圈状复合物一侧的中央腔内相互作用。碱基通过堆积作用以及在古细菌和真核生物Sm蛋白中高度保守的残基所构成的口袋中的特异性氢键接触相结合,而磷酸基团仍可接触溶剂。与人类Sm蛋白二聚体结构的比较揭示了密切相关的单体折叠和亚基间接触,表明Sm核心结构域的结构和RNA结合在进化过程中得以保留。