Crystal structures of the thi-box riboswitch bound to thiamine pyrophosphate analogs reveal adaptive RNA-small molecule recognition
Crystal structures of the thi-box riboswitch bound to thiamine pyrophosphate analogs reveal adaptive RNA-small molecule recognition
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DOI：
10.1016/j.str.2006.07.008
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发表时间：
2006-09-01
期刊：
影响因子：
5.7
通讯作者：
Ferre-D'Amare, Adrian R.
中科院分区：
文献类型：
--
作者：
Edwards, Thomas E.;Ferre-D'Amare, Adrian R.
核糖开关是一种非编码的mRNA元件，它能以高亲和力和特异性结合小分子代谢物，并调节相关基因的表达。硫盒核糖开关对硫胺素焦磷酸的亲和力比对密切相关的非同源化合物（如硫胺素一磷酸）高1000倍。为了理解硫盒对硫胺素焦磷酸特异性的化学基础，我们测定了大肠杆菌硫盒与硫胺素焦磷酸、硫胺素一磷酸以及结构类似物苯磷硫胺和吡啶硫胺结合的晶体结构。当与单磷酸化化合物结合时，识别配体的硫胺素和磷酸部分的RNA元件会靠得更近。这使得核糖开关能够以类似于识别硫胺素焦磷酸的β -磷酸的方式识别一磷酸。在吡啶硫胺复合物中，焦磷酸结合位点在很大程度上是无结构的。这些结果展示了核糖开关如何与各种代谢物结合，以及硫盒为什么优先结合硫胺素焦磷酸。
Riboswitches are noncoding mRNA elements that bind small-molecule metabolites with high affinity and specificity, and they regulate the expression of associated genes. The thi-box riboswitch can exhibit a 1000-fold higher affinity for thiamine pyrophosphate over closely related noncognate compounds such as thiamine monophosphate. To understand the chemical basis of thi-box pyrophosphate specificity, we have determined crystal structures of an E. coli thi-box bound to thiamine pyrophosphate, thiamine monophosphate, and the structural analogs benfotiamine and pyrithiamine. When bound to monophosphorylated compounds, the RNA elements that recognize the thiamine and phosphate moieties of the ligand move closer together. This allows the riboswitch to recognize the monophosphate in a manner similar to how it recognizes the beta-phosphate of thiamine pyrophosphate. In the pyrithiamine complex, the pyrophosphate binding site is largely unstructured. These results show how the riboswitch can bind to various metabolites, and why the thi-box preferentially binds thiamine pyrophosphate.