Ligand-induced folding of the adenosine deaminase A-riboswitch and implications on riboswitch translational control
Ligand-induced folding of the adenosine deaminase A-riboswitch and implications on riboswitch translational control
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DOI：
10.1002/cbic.200700057
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发表时间：
2007-05-25
期刊：
影响因子：
3.2
通讯作者：
Micura, Ronald
中科院分区：
文献类型：
--
作者：
Rieder, Renate;Lang, Kathrin;Micura, Ronald
通过使用基于结构的荧光光谱方法，我们研究了调节翻译起始的腺嘌呤反应性核糖开关的折叠。我们观察到这种配体对创伤弧菌腺苷脱氨酶（add） mRNA适配体结构域的适应性识别，甚至在远离结合位点的预组织环环区域也发现了明显的构象变化。重要的是，全长核糖开关结构域具有潜在的翻译抑制因子，能够与腺嘌呤形成二元复合体，而不作为折叠陷阱来抑制结合。因此，通过表达平台扩展的适体对其配体保持完全响应；这与先前研究的pbuE A核糖开关相反，后者被困在无响应性终止褶中。因此，后者必须采用复杂的反应机制，如在动力学控制模式下操作或使用转录暂停，为适体部分折叠和结合提供时间。核开关的不同行为可以通过它们在适体和表达平台之间的不同序列接口来合理化。对于添加a -核糖开关，我们的数据表明了一个热力学驱动的响应机制。
By using a structure-based fluorescence spectroscopic approach, we have examined the folding of an adenine-responsive riboswitch that regulates translational initiation. We observed adaptive recognition of the ligand for the aptamer domain of adenosine deaminase (add) mRNA from Vibrio vulnificus, and revealed pronoundced conformational changes even in the preorganized loop-loop region that is distant from the binding site. Importantly, the full-length riboswitch domain, which has a potential translational repressor stem is able to form a binary complex with adenine, and does not act as a folding trap to inhibit binding. The aptamer that is extended by the expression platform therefore remains fully responsive to its ligand; this is in contrast to the previously investigated pbuE A riboswitch, which becomes trapped in a nonresponsiveness terminator fold. Consequently, the latter must employ complex response mechanisms, such as operating in kinetic-control mode or using transcriptional pausing, to provide time for aptamer portion to fold and to bind. The different behaviour of the riboswitches can be rationalized by their distinct sequence interface between the aptamer and expression platform. For the add A-riboswitch, our data suggest a thermodynamically driven response mechanism.