THE CONFORMATION OF THE SARCIN RICIN LOOP FROM 28S RIBOSOMAL-RNA
THE CONFORMATION OF THE SARCIN RICIN LOOP FROM 28S RIBOSOMAL-RNA
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DOI：
10.1073/pnas.90.20.9581
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发表时间：
1993-10-15
影响因子：
11.1
通讯作者：
WOOL, IG
中科院分区：
文献类型：
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作者：
SZEWCZAK, AA;MOORE, PB;WOOL, IG
八叠球菌毒素/蓖麻毒素环是在所有大核糖体亚基的RNA中发现的高度保守序列。细胞毒素α-八叠球菌素和蓖麻毒素都通过切割核糖体环中的一个单键来破坏核糖体。一旦它被攻击，核糖体不再与延伸因子正确地相互作用，翻译停止。我们已经确定了多核NMR光谱使用E73，29个核苷酸的RNA，具有的八叠球菌毒素/蓖麻毒素环序列，是敏感的毒素在体外的八叠球菌毒素/蓖麻毒素环的构象。八叠球菌素/蓖麻毒素环具有紧凑的结构，其包含几个嘌呤碱基对、一个GAGA四环和一个邻近反向Hoogsteen A.U对的凸出的鸟苷。它是由一组不寻常的跨链碱基堆积相互作用和亚氨基质子磷酸氧氢键稳定。除了具有有趣的结构特征外，该模型还解释了许多关于环结构及其与细胞毒素的反应性的生化观察，并揭示了环与延伸因子的相互作用。
The sarcin/ricin loop is a highly conserved sequence found in the RNA of all large ribosomal subunits. The cytotoxins alpha-sarcin and ricin both inactivate ribosomes by cleaving a single bond in that loop. Once it has been attacked, ribosomes no longer interact with elongation factors properly, and translation stops. We have determined the conformation of the sarcin/ricin loop by multinuclear NMR spectroscopy using E73, a 29-nucleotide RNA that has the sarcin/ricin loop sequence and that is sensitive to both toxins in vitro. The sarcin/ricin loop has a compact structure that contains several purine.purine base pairs, a GAGA tetraloop, and a bulged guanosine adjacent to a reverse Hoogsteen A.U pair. It is stabilized by an unusual set of cross-strand base-stacking interactions and imino proton to phosphate oxygen hydrogen bonds. In addition to having interesting structural features, this model explains many of the biochemical observations made about the loop's structure and its reactivity with cytotoxins, and it sheds light on the loop's interactions with elongation factors.