García-Marcos Alberto, Morreale Antonio, Guarinos Esther, Briones Elisa, Remacha Miguel, Ortiz Angel R, Ballesta Juan P G
Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid and Consejo Superior de investigaciones Científicas, Cantoblanco, Madrid 28049, Spain.
Nucleic Acids Res. 2007;35(21):7109-17. doi: 10.1093/nar/gkm773. Epub 2007 Oct 16.
Eukaryotic ribosomal stalk protein L12 and its bacterial orthologue L11 play a central role on ribosomal conformational changes during translocation. Deletion of the two genes encoding L12 in Saccharomyces cerevisiae resulted in a very slow-growth phenotype. Gene RPL12B, but not the RPL12A, cloned in centromeric plasmids fully restored control protein level and the growth rate when expressed in a L12-deprived strain. The same strain has been transformed to express Escherichia coli protein EcL11 under the control of yeast RPL12B promoter. The bacterial protein has been found in similar amounts in washed ribosomes from the transformed yeast strain and from control E. coli cells, however, EcL11 was unable to restore the defective acidic protein stalk composition caused by the absence of ScL12 in the yeast ribosome. Protein EcL11 induced a 10% increase in L12-defective cell growth rate, although the in vitro polymerizing capacity of the EcL11-containing ribosomes is restored in a higher proportion, and, moreover, the particles became partially sensitive to the prokaryotic specific antibiotic thiostrepton. Molecular dynamic simulations using modelled complexes support the correct assembly of bacterial L11 into the yeast ribosome and confirm its direct implication of its CTD in the binding of thiostrepton to ribosomes.
真核生物核糖体柄蛋白L12及其细菌同源物L11在转位过程中的核糖体构象变化中起核心作用。在酿酒酵母中缺失编码L12的两个基因会导致生长非常缓慢的表型。当在缺乏L12的菌株中表达时,克隆在着丝粒质粒中的基因RPL12B而非RPL12A能完全恢复对照蛋白水平和生长速率。已将同一菌株转化为在酵母RPL12B启动子的控制下表达大肠杆菌蛋白EcL11。在转化酵母菌株和对照大肠杆菌细胞的洗涤核糖体中发现了相似量的细菌蛋白,然而,EcL11无法恢复酵母核糖体中因缺乏ScL12而导致的有缺陷的酸性蛋白柄组成。蛋白EcL11使L12缺陷细胞的生长速率提高了10%,尽管含EcL11的核糖体的体外聚合能力以更高的比例恢复,而且,这些颗粒对原核生物特异性抗生素硫链丝菌素变得部分敏感。使用建模复合物进行的分子动力学模拟支持细菌L11正确组装到酵母核糖体中,并证实其C末端直接参与硫链丝菌素与核糖体的结合。