Structural basis for discriminative regulation of gene expression by adenine- and guanine-sensing mRNAs
Structural basis for discriminative regulation of gene expression by adenine- and guanine-sensing mRNAs
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DOI：
10.1016/j.chembiol.2004.11.018
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发表时间：
2004-12-01
影响因子：
--
通讯作者：
Patel, DJ
中科院分区：
文献类型：
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作者：
Serganov, A;Yuan, YR;Patel, DJ
代谢物敏感的mRNAs，或“核糖开关”，专门与小配体相互作用，并直接表达涉及其新陈代谢的基因。核糖开关含有感应“适配子”模块，能够引起配体诱导的结构变化，以及下游区域，含有表达控制元件。我们报道了Add A-核糖开关和XPT G-核糖开关适配子模块的晶体结构，它们以精致的特异性区分结合腺嘌呤和鸟嘌呤，并调节两组不同基因的表达。核糖开关形成音叉状结构，其中尖端通过发夹环相互作用平行保持，内部气泡拉链向上形成嘌呤结合口袋。结合的嘌呤是通过氢键相互作用而保持的，这些氢键作用涉及整个外围的保守核苷酸。识别特异性与被包裹的腺嘌呤和鸟嘌呤配体分别与尿苷和胞嘧啶配对有关。
Metabolite-sensing mRNAs, or "riboswitches," specifically interact with small ligands and direct expression of the genes involved in their metabolism. Riboswitches contain sensing "aptamer" modules, capable of ligand-induced structural changes, and downstream regions, harboring expression-controlling elements. We report the crystal structures of the add A-riboswitch and xpt G-riboswitch aptamer modules that distinguish between bound adenine and guanine with exquisite specificity and modulate expression of two different sets of genes. The riboswitches form tuning fork-like architectures, in which the prongs are held in parallel through hairpin loop interactions, and the internal bubble zippers up to form the purine binding pocket. The bound purines are held by hydrogen bonding interactions involving conserved nucleotides along their entire periphery. Recognition specificity is associated with Watson-Crick pairing of the encapsulated adenine and guanine ligands with uridine and cytosine, respectively.