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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >An intermolecular base triple as the basis of ligand specificity and affinity in the guanine- and adenine-sensing riboswitch RNAs.
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An intermolecular base triple as the basis of ligand specificity and affinity in the guanine- and adenine-sensing riboswitch RNAs.

机译：分子间碱基三倍体是鸟嘌呤和腺嘌呤敏感核糖开关RNA中配体特异性和亲和力的基础。

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摘要

Riboswitches are highly structured RNA elements that control the expression of many bacterial genes by binding directly to small metabolite molecules with high specificity and affinity. In Bacillus subtilis, two classes of riboswitches have been described that discriminate between guanine and adenine despite an extremely high degree of homology both in their primary and secondary structure. We have identified intermolecular base triples between both purine ligands and their respective riboswitch RNAs by NMR spectroscopy. Here, specificity is mediated by the formation of a Watson-Crick base pair between the guanine ligand and a C residue or the adenine ligand and a U residue of the cognate riboswitch RNA, respectively. In addition, a second base-pairing interaction common to both riboswitch purine complexes involves a uridine residue of the RNA and the N3/N9 edge of the purine ligands. This base pairing is mediated by a previously undescribed hydrogen-bonding scheme that contributes to the affinity of the RNA-ligand interaction. The observed intermolecular hydrogen bonds between the purine ligands and the RNA rationalize the previously observed change in specificity upon a C to U mutation in the core of the purine riboswitch RNAs and the differences in the binding affinities for a number of purine analogs.
机译：核糖开关是高度结构化的RNA元件，通过直接结合具有高特异性和亲和力的小代谢物分子来控制许多细菌基因的表达。在枯草芽孢杆菌中，已经描述了两类核糖开关，尽管它们的一级和二级结构具有极高的同源性，但它们可区分鸟嘌呤和腺嘌呤。我们已经确定了两个分子之间嘌呤配体和它们各自的核糖开关RNA之间的分子间碱基三重核磁共振波谱。在此，特异性是通过在同源核糖开关RNA的鸟嘌呤配体和C残基或腺嘌呤配体和U残基之间形成沃森-克里克碱基对来介导的。另外，两个核糖开关嘌呤复合物共有的第二个碱基配对相互作用涉及RNA的尿苷残基和嘌呤配体的N3 / N9边缘。该碱基对由先前未描述的氢键方案介导，该氢键方案有助于RNA-配体相互作用的亲和力。嘌呤配体和RNA之间观察到的分子间氢键使先前观察到的嘌呤核糖开关RNA核心中C到U突变的特异性变化以及许多嘌呤类似物的结合亲和力差异合理化。

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