Structure of a natural guanine-responsive riboswitch complexed with the metabolite hypoxanthine
Structure of a natural guanine-responsive riboswitch complexed with the metabolite hypoxanthine
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DOI：
10.1038/nature03037
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发表时间：
2004-11-18
期刊：
影响因子：
64.8
通讯作者：
Montange, RK
中科院分区：
文献类型：
--
作者：
Batey, RT;Gilbert, SD;Montange, RK
核糖开关是在信使RNA的50个非翻译区发现的遗传调控元件，在缺乏蛋白质辅助因子的情况下起作用（1,2）。它们广泛分布在细菌中，占枯草芽孢杆菌所有基因的2%以上，强调了它们在控制细胞代谢中的重要性(3)。许多参与嘌呤代谢和转运的基因的mrna的5'非翻译区含有一个鸟嘌呤响应核糖体开关，直接结合鸟嘌呤、次黄嘌呤或黄嘌呤来终止转录（3,4）。在这里，我们报道了在1.95埃分辨率下，枯草芽孢杆菌xpx - pbux操纵子的鸟嘌呤核糖开关与次黄嘌呤结合的晶体结构，次黄嘌呤是细菌嘌呤回收途径中的一种常见代谢物。这种结构揭示了一个复杂的RNA折叠，涉及几个系统发育上保守的核苷酸，这些核苷酸产生一个几乎完全包裹配体的结合袋。次黄嘌呤的作用是稳定这种结构，促进下游转录终止元件的形成，从而提供了一种直接抑制细胞内代谢物浓度增加时基因表达的机制。
Riboswitches are genetic regulatory elements found in the 50 untranslated region of messenger RNA that act in the absence of protein cofactors(1,2). They are broadly distributed across bacteria and account for the regulation of more than 2% of all genes in Bacillus subtilis, underscoring their importance in the control of cellular metabolism(3). The 5' untranslated region of many mRNAs of genes involved in purine metabolism and transport contain a guanine-responsive riboswitch that directly binds guanine, hypoxanthine or xanthine to terminate transcription(3,4). Here we report the crystal structure at 1.95 Angstrom resolution of the purine-binding domain of the guanine riboswitch from the xpt-pbuX operon of B. subtilis bound to hypoxanthine, a prevalent metabolite in the bacterial purine salvage pathway. This structure reveals a complex RNA fold involving several phylogenetically conserved nucleotides that create a binding pocket that almost completely envelops the ligand. Hypoxanthine functions to stabilize this structure and to promote the formation of a downstream transcriptional terminator element, thereby providing a mechanism for directly repressing gene expression in response to an increase in intracellular concentrations of metabolite.