Riboswitch function: flipping the switch or tuning the dimmer?
Riboswitch function: flipping the switch or tuning the dimmer?
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DOI：
10.4161/rna.7.3.11932
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发表时间：
2010-05
期刊：
影响因子：
4.1
通讯作者：
Ferré-D'Amaré AR
中科院分区：
文献类型：
--
作者：
Baird NJ;Kulshina N;Ferré-D'Amaré AR
核糖开关是参与基因调控的结构化mRNA元件，对细胞内特定小分子的浓度作出反应。除了调节结合位点的精细结构外，它们的同源配体的结合被认为会引起核糖开关的全局构象变化。x射线晶体学已经对几种核开关的配体结合构象的三维结构进行了详细的描述。我们利用小角度x射线散射（SAXS）对响应焦磷酸硫胺素（TPP）和细菌第二信使环二胍酸酯（c-di-GMP）的核糖开关的配体结合域的无配体状态进行了低分辨率重建。SAXS重建与这两种核开关晶体结构的比较表明，rna经历了剧烈的配体诱导的全局构象变化。然而，这并不是核糖开关的普遍特征。SAXS分析了几种其他核素开关配体结合域的溶液行为，证明了广泛的构象开关行为，从TPP和c-二- gmp核素开关的明确开关到黄素单核苷酸（FMN）核素开关的完全无开关。此外，来自不同生物体的相同核糖开关的开关行为在不同的例子之间是不同的。观察到的行为范围表明，为了响应精确遗传调控的进化需要，核糖开关可能被调整为更像调光器或变阻器，而不是二元开/关开关。
Riboswitches are structured mRNA elements involved in gene regulation that respond to the intracellular concentration of specific small molecules. Binding of their cognate ligand is thought to elicit a global conformational change of the riboswitch, in addition to modulating the fine structure of the binding site. X-ray crystallography has produced detailed descriptions of the three-dimensional structures of the ligand-bound conformations of several riboswitches. We have employed small-angle X-ray scattering (SAXS) to generate low-resolution reconstructions of the ligand-free states of the ligand-binding domains of riboswitches that respond to thiamine pyrophosphate (TPP), and cyclic diguanylate (c-di-GMP), a bacterial second messenger. Comparison of the SAXS reconstructions with the crystal structures of these two riboswitches demonstrates that the RNAs undergo dramatic ligand-induced global conformational changes. However, this is not an universal feature of riboswitches. SAXS analysis of the solution behavior of several other riboswitch ligand-binding domains demonstrates a broad spectrum of conformational switching behaviors, ranging from the unambiguous switching of the TPP and c-di-GMP riboswitches to complete lack of switching for the flavin mononucleotide (FMN) riboswitch. Moreover, the switching behavior varies between examples of the same riboswitch from different organisms. The range of observed behaviors suggests that in response to the evolutionary need for precise genetic regulation, riboswitches may be tuned to function more as dimmers or rheostats than binary on/off switches.
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影响因子：
9.8
作者：
De N;Pirruccello M;Krasteva PV;Bae N;Raghavan RV;Sondermann H
通讯作者：
Sondermann H
影响因子：
64.8
作者：
Barends, Thomas R. M.;Hartmann, Elisabeth;Schlichting, Ilme
通讯作者：
Schlichting, Ilme
影响因子：
64.8
作者：
Batey, RT;Gilbert, SD;Montange, RK
通讯作者：
Montange, RK
影响因子：
56.9
作者：
Klein, Daniel J.;Ferre-D'Amare, Adrian R.
通讯作者：
Ferre-D'Amare, Adrian R.
影响因子：
5.7
作者：
Edwards, Thomas E.;Ferre-D'Amare, Adrian R.
通讯作者：
Ferre-D'Amare, Adrian R.