Metal-ion binding and metal-ion induced folding of the adenine-sensing riboswitch aptamer domain.
Metal-ion binding and metal-ion induced folding of the adenine-sensing riboswitch aptamer domain.
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腺嘌呤感应核糖开关适体结构域的金属离子结合和金属离子诱导折叠。
DOI：
10.1093/nar/gkm565
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发表时间：
2007
影响因子：
14.9
通讯作者：
Wöhnert J
中科院分区：
文献类型：
--
作者：
Noeske J;Schwalbe H;Wöhnert J
二价阳离子在复杂RNA结构的折叠和稳定中是重要的。腺嘌呤感应核糖开关通过直接感应细胞内腺嘌呤水平来控制参与嘌呤代谢的蛋白质的mRNA表达。腺嘌呤以高亲和力和特异性结合腺嘌呤敏感核糖开关的配体结合或适体结构域。该结构域与腺嘌呤复合的X射线结构揭示了一个复杂的RNA折叠，由长距离碱基配对相互作用稳定的三螺旋连接组成，并确定了六水合Mg 2+离子的5个结合位点。此外，Mg2+离子在配体诱导的折叠的RNA的作用被建议。在这里，我们描述了二价阳离子与RNA-腺嘌呤复合物在溶液中的相互作用，通过高分辨率NMR光谱研究。顺磁性谱线增宽、化学位移作图和分子间核奥弗豪泽效应（NOEs）表明，二价阳离子至少存在三个结合位点。其中两个与X射线结构中的结构相似。第三个位点，这是重要的折叠这种RNA，以前没有观察到。RNA的无配体状态在构象上是异质的，并且含有在不存在Mg 2+的情况下对配体结合有害的碱基配对模式，但是在Mg 2+的存在下变得部分预组织用于配体结合。与高度相似的鸟嘌呤敏感核糖开关相比，腺嘌呤敏感核糖开关适体结构域的折叠途径更复杂，Mg 2+的影响更明显。
Divalent cations are important in the folding and stabilization of complex RNA structures. The adenine-sensing riboswitch controls the expression of mRNAs for proteins involved in purine metabolism by directly sensing intracellular adenine levels. Adenine binds with high affinity and specificity to the ligand binding or aptamer domain of the adenine-sensing riboswitch. The X-ray structure of this domain in complex with adenine revealed an intricate RNA-fold consisting of a three-helix junction stabilized by long-range base-pairing interactions and identified five binding sites for hexahydrated Mg2+-ions. Furthermore, a role for Mg2+-ions in the ligand-induced folding of this RNA was suggested. Here, we describe the interaction of divalent cations with the RNA–adenine complex in solution as studied by high-resolution NMR spectroscopy. Paramagnetic line broadening, chemical shift mapping and intermolecular nuclear Overhauser effects (NOEs) indicate the presence of at least three binding sites for divalent cations. Two of them are similar to those in the X-ray structure. The third site, which is important for the folding of this RNA, has not been observed previously. The ligand-free state of the RNA is conformationally heterogeneous and contains base-pairing patterns detrimental to ligand binding in the absence of Mg2+, but becomes partially pre-organized for ligand binding in the presence of Mg2+. Compared to the highly similar guanine-sensing riboswitch, the folding pathway for the adenine-sensing riboswitch aptamer domain is more complex and the influence of Mg2+ is more pronounced.
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影响因子：
14.9
作者：
ALLAIN, FHT;VARANI, G
通讯作者：
VARANI, G
影响因子：
3.2
作者：
Rieder, Renate;Lang, Kathrin;Micura, Ronald
通讯作者：
Micura, Ronald
影响因子：
2.7
作者：
BARTELS, C;XIA, TH;WUTHRICH, K
通讯作者：
WUTHRICH, K
影响因子：
16.8
作者：
Mandal, M;Breaker, RR
通讯作者：
Breaker, RR
影响因子：
64.8
作者：
Batey, RT;Gilbert, SD;Montange, RK
通讯作者：
Montange, RK