Metabolite recognition principles and molecular mechanisms underlying riboswitch function.
Metabolite recognition principles and molecular mechanisms underlying riboswitch function.
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DOI：
10.1146/annurev-biophys-101211-113224
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发表时间：
2012
影响因子：
12.4
通讯作者：
Patel DJ
中科院分区：
文献类型：
--
作者：
Serganov A;Patel DJ
核糖开关是一种mRNA元件，能够调节基因的表达，以响应细胞代谢物的特定结合。核糖开关通过代谢产物感受域的非配体构象和配基结合构象相互作用，进而调节相邻基因表达调控元件的形成。X射线结晶学和核磁共振光谱已经确定了几乎所有主要的核糖开关类在配体结合状态下的三维结构，对于一些核糖开关来说，在无配体状态下。由此产生的空间拓扑结构展示了核糖开关折叠的广泛多样性，并揭示了同源代谢物特定识别的结构原理。现有的三维信息，辅以结构引导的生物物理和生化实验，使人们更好地理解了核糖开关是如何折叠的，配体识别需要什么RNA构象，以及配体结合如何转化为基因表达调控。这些研究极大地促进了对核糖开关作用的分子机制的剖析，并反过来应该指导操纵基因调控电路的工具的预期发展。
Riboswitches are mRNA elements capable of modulating gene expression in response to specific binding by cellular metabolites. Riboswitches exert their function through the interplay of alternative ligand-free and ligand-bound conformations of the metabolite-sensing domain, which in turn modulate the formation of adjacent gene expression controlling elements. X-ray crystallography and NMR spectroscopy have determined three-dimensional structures of virtually all the major riboswitch classes in the ligand-bound state and, for several riboswitches, in the ligand-free state. The resulting spatial topologies have demonstrated the wide diversity of riboswitch folds and revealed structural principles for specific recognition by cognate metabolites. The available three-dimensional information, supplemented by structure-guided biophysical and biochemical experimentation, has led to an improved understanding of how riboswitches fold, what RNA conformations are required for ligand recognition, and how ligand binding can be transduced into gene expression modulation. These studies have greatly facilitated the dissection of molecular mechanisms underlying riboswitch action and should in turn guide the anticipated development of tools for manipulating gene regulatory circuits.