Drygin D, Zimmermann R A
Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst 01003-4505, USA.
RNA. 2000 Dec;6(12):1714-26. doi: 10.1017/s1355838200001436.
The complex of ribosomal protein L1 with 23S rRNA from Escherichia coli is of great interest because of the unique structural and functional aspects of this ribonucleoprotein domain. We have minimized the binding site for protein L1 on the 23S rRNA to nt 2120-2129, 2159-2162, and 2167-2178. This RNA fragment consists of two helices as well as an interconnecting loop of unknown structure. RNA molecules corresponding to the minimized L1 binding site, in which G, A, U, or C were individually replaced by their deoxyribo- (dN) or alpha-thio- (rNaS) analogs have been synthesized by T7 transcription in vitro and analyzed for their ability to bind protein L1. It has been demonstrated that the substitution of rNaS at position 2122 or 2176 decreases the affinity of the RNA for the protein in the presence of magnesium five- to tenfold, whereas the same changes have little effect on binding in the presence of manganese. This suggests that Rp oxygens in the phosphates preceding positions 2122 and 2176 are coordinated with Mg2+ and may participate in L1-23S rRNA interaction via magnesium bridges. We have also shown that this interaction is impaired by the presence of dC at position 2122 coupled with the presence of deoxyribonucleotide(s) at other positions in the RNA. This study demonstrates that the ribose-phosphate backbone of the helix encompassing nt 2120-2124/2174-2178 is intimately involved in the interaction of protein L1 with the 23S rRNA. In particular, we suggest that this helix is positioned in the cleft between the two domains of protein L1.
大肠杆菌核糖体蛋白L1与23S rRNA形成的复合物备受关注,因为该核糖核蛋白结构域具有独特的结构和功能特性。我们已将23S rRNA上蛋白L1的结合位点最小化至核苷酸2120 - 2129、2159 - 2162和2167 - 2178。该RNA片段由两个螺旋以及一个结构未知的连接环组成。通过体外T7转录合成了与最小化L1结合位点对应的RNA分子,其中G、A、U或C分别被其脱氧核糖(dN)或α-硫代(rNaS)类似物取代,并分析了它们结合蛋白L1的能力。结果表明,在存在镁的情况下,2122位或2176位的rNaS取代会使RNA与蛋白的亲和力降低五到十倍,而在存在锰的情况下,相同变化对结合影响不大。这表明2122位和2176位之前磷酸酯中的核糖氧与Mg2+配位,并可能通过镁桥参与L1 - 23S rRNA相互作用。我们还表明,2122位存在dC并伴有RNA其他位置存在脱氧核苷酸时,这种相互作用会受到损害。这项研究表明,包含核苷酸2120 - 2124/2174 - 2178的螺旋的核糖磷酸骨架密切参与蛋白L1与23S rRNA的相互作用。特别是,我们认为该螺旋位于蛋白L1两个结构域之间的裂隙中。