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Coenzyme Recognition And Gene Regulation By A Flavin Mononucleotide Riboswitch

机译：黄素单核苷酸核糖开关对辅酶的识别和基因调控

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摘要

The biosynthesis of several protein cofactors is subject to feedback regulation by riboswitches. Flavin mononucleotide (FMN)-specific riboswitches, also known as RFN elements, direct expression of bacterial genes involved in the biosynthesis and transport of riboflavin (vitamin B_2) and related compounds. Here we present the crystal structures of the Fusobacterium nucleatum riboswitch bound to FMN, riboflavin and antibiotic roseoflavin. The FMN riboswitch structure, centred on an FMN-bound six-stem junction, does not fold by collinear stacking of adjacent helices, typical for folding of large RNAs. Rather, it adopts a butterfly-like scaffold, stapled together by opposingly directed but nearly identically folded peripheral domains. FMN is positioned asymmetrically within the junctional site and is specifically bound to RNA through interactions with the isoalloxazine ring chromophore and direct and Mg~(2+)-mediated contacts with the phosphate moiety. Our structural data, complemented by binding and footprinting experiments, imply a largely pre-folded tertiary RNA architecture and FMN recognition mediated by conformational transitions within the junctional binding pocket. The inherent plasticity of the FMN-binding pocket and the availability of large openings make the riboswitch an attractive target for structure-based design of FMN-like antimicrobial compounds. Our studies also explain the effects of spontaneous and antibiotic-induced deregulatory mutations and provided molecular insights into FMN-based control of gene expression in normal and riboflavin-overproducing bacterial strains.
机译：几种蛋白质辅因子的生物合成受核糖开关的反馈调节。黄素单核苷酸（FMN）特定的核糖开关，也称为RFN元件，直接表达参与核黄素（维生素B_2）和相关化合物的生物合成和运输的细菌基因。在这里，我们介绍与FMN，核黄素和抗生素玫瑰黄素结合的核梭状芽孢杆菌核糖开关的晶体结构。 FMN核糖开关结构以FMN绑定的六茎结为中心，不会通过相邻螺旋的共线堆叠而折叠，这通常是折叠大RNA的典型方式。相反，它采用了蝴蝶状的支架，该支架通过相对指向但几乎相同折叠的外围区域钉在一起。 FMN不对称地位于连接位点内，并通过与异四恶嗪环生色团的相互作用以及与Mg〜（2+）介导的与磷酸盐部分的直接接触而与RNA特异性结合。我们的结构数据，结合和足迹实验的补充，暗示在很大程度上是折叠前的三级RNA结构和FMN识别由连接结合袋内的构象转换介导。 FMN结合袋的固有可塑性和大开口的可用性使核糖开关成为FMN类抗菌化合物基于结构设计的有吸引力的目标。我们的研究还解释了自发和抗生素诱导的失调突变的影响，并为基于FMN的正常和生产核黄素的细菌菌株中基因表达的控制提供了分子见解。

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  • 来源
    《Nature》 |2009年第7235期|p.233-237|共5页
  • 作者

    Alexander Serganov; Lili Huang; Dinshaw J. Patel;

  • 作者单位

    Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 自然科学总论;
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