Structural biology of riboswitch-mediated gene regulation and argonaute-mediated gene silencing.
Structural biology of riboswitch-mediated gene regulation and argonaute-mediated gene silencing.
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核糖开关介导的基因调控和阿尔古特介导的基因沉默的结构生物学。
DOI：
10.1093/nass/nrn001
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Patel,DinshawJ
中科院分区：
文献类型：
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作者：
Patel,DinshawJ
细菌 mRNA 的 5'-非翻译区可以充当分子传感器，通过适当调节控制代谢物合成、运输和降解的基因的表达来响应代谢物浓度的波动。这种核糖开关由代谢物传感和表达平台结构域组成，传感结构域由高度保守的序列和结构元件组成，这些结构元件是生成与特定代谢物识别和密切相关类似物的识别相关的结合袋所需的。我课题组的Alexander Serganov和Lily Huang解决了两个新型大型核糖开关的代谢物传感结构域的结合态的晶体结构。每个传感域的二级结构包含多螺旋连接，涉及大的内部气泡，在复杂的形成上形成紧凑的支架。复合物的结构解决了以下问题：复合物形成时螺旋茎的同轴排列模式是什么？稳定整体架构的环-环和环-受体相互作用的模式是什么？结合袋是否位于多茎连接位点，如果是，有多少连接核苷酸参与形成结合袋，它们是否源自内部气泡的不同片段？配体是否以延伸或折叠构象结合在复合物中，RNA 支架内是否存在供其进入和释放的途径？带电配体如何被各自的 RNA 支架识别？离子在介导识别中的作用是什么？人们可以在多大程度上设计和测试配体类似物调节相互作用特异性的能力？
The 5′-untranslated regions of bacterial mRNAs can act as molecular sensors, responding to fluctuating metabolite concentrations by appropriate modulation of the expression of genes governing metabolite synthesis, transport and degradation. Such riboswitches are composed of metabolite-sensing and expression platform domains, with the sensing domain composed of highly conserved sequence and structural elements required for generation of binding pockets associated with specific metabolite recognition and discrimination against closely related analogs.Alexander Serganov and Lily Huang in my group have solved the crystal structures of the bound state of the metabolite-sensing domains of two new large riboswitches. The secondary structure of each sensing domain contains multi-helical junctions involving large internal bubbles that form compact scaffolds on complex formation. The structures of the complexes address the following questions: What is the pattern of coaxial alignment of helical stems on complex formation? What is the pattern of loop-loop and loop-receptor interactions stabilizing the overall architecture? Are the binding pockets located at the multistem junctional site, and if so, how many junctional nucleotides are involved in forming the binding pocket and do they originate from different segments of the internal bubble? Do the ligands bind in an extended or fold-back conformation in the complex and does a pathway exist within the RNA scaffold for their entry and release? How are the charged ligands recognized by their respective RNA scaffolds and what is the role of ions in mediating recognition? To what extent can one design and test analogs of the ligands for their ability to modulate interaction specificity?