The structure of a tetrahydrofolate-sensing riboswitch reveals two ligand binding sites in a single aptamer.

The structure of a tetrahydrofolate-sensing riboswitch reveals two ligand binding sites in a single aptamer.
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DOI:
10.1016/j.str.2011.06.019
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发表时间:
2011-10-12
期刊:
影响因子:
5.7
通讯作者:
Batey, Robert T.
Batey, Robert T.
中科院分区:
生物学2区
文献类型:
--
作者:
Trausch, Jeremiah J.;Ceres, Pablo;Reyes, Francis E.;Batey, Robert T.

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叶酸及其衍生物的运输和生物合成通常受四氢叶酸(THF)核糖开关的控制。我们已经解决了四氢呋喃核糖开关适配子与四氢呋喃类似物叶酸的络合物的晶体结构。独特的是,这种结构揭示了两个叶酸分子结合到一个结构域上。这两个位点以相似的方式与配体相互作用,主要是通过识别减少的蝶呤蛋白部分。7-去氮鸟嘌呤是鸟嘌呤的一种可溶类似物,它与核糖开关结合的亲和力与其天然效应物几乎相同。然而,7-去氮鸟嘌呤对转录终止的影响要比叶酸小得多,这表明细胞内的鸟嘌呤池并不作用于THF核糖开关。在生理条件下,配体表现出很强的协同结合,两个位点中的一个在诱导调控反应中发挥了更大的作用,这表明第二个位点可能发挥另一种功能。
Transport and biosynthesis of folate and its derivatives is frequently controlled by the tetrahydrofolate (THF) riboswitch in Firmicutes. We have solved the crystal structure of the THF riboswitch aptamer in complex with folinic acid, a THF analog. Uniquely, this structure reveals two molecules of folinic acid binding to a single structured domain. These two sites interact with ligand in a similar fashion, primarily through recognition of the reduced pterin moiety. 7-deazaguanine, a soluble analog of guanine, binds the riboswitch with nearly the same affinity as its natural effector. However, 7-deazaguanine effects transcriptional termination to a substantially lesser degree than folinic acid, suggesting that the cellular guanine pool does not act upon the THF riboswitch. Under physiological conditions the ligands display strong cooperative binding, with one of the two sites playing a greater role in eliciting the regulatory response, which suggests that the second site may play another functional role.
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