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Convergent Use of Heptacoordination for Cation Selectivity by RNA and Protein Metalloregulators.
Cell Chemical Biology ( IF 8.6 ) Pub Date : 2018-05-24 , DOI: 10.1016/j.chembiol.2018.04.016
Sharrol T Bachas 1 , Adrian R Ferré-D'Amaré 1
Affiliation  

The large yybP-ykoY family of bacterial riboswitches is broadly distributed phylogenetically. Previously, these gene-regulatory RNAs were proposed to respond to Mn2+. X-ray crystallography revealed a binuclear cation-binding pocket. This comprises one hexacoordinate site, with six oxygen ligands, which preorganizes the second, with five oxygen and one nitrogen ligands. The relatively soft nitrogen ligand was proposed to confer affinity for Mn2+, but how this excludes other soft cations remained enigmatic. By subjecting representative yybP-ykoY riboswitches to diverse cations in vitro, we now find that these RNAs exhibit limited transition metal ion selectivity. Among the cations tested, Cd2+ and Mn2+ bind most tightly, and comparison of three new Cd2+-bound crystal structures suggests that these riboswitches achieve selectivity by enforcing heptacoordination (favored by high-spin Cd2+ and Mn2+, but otherwise uncommon) in the softer site. Remarkably, the Cd2+- and Mn2+-selective bacterial transcription factor MntR also uses heptacoordination within a binuclear site to achieve selectivity.

中文翻译:

RNA和蛋白质金属调节剂在庚酸配位中对阳离子选择性的融合应用。

细菌核糖开关的大型yybP-ykoY家族在系统发育上分布广泛。以前,这些基因调节的RNA提出了对Mn2 +的反应。X射线晶体学显示双核阳离子结合袋。它包含一个带有六个氧配体的六配位位点,该位点将第二个带有五个氧和一个氮配体的预配位基进行了组织。提出了相对较软的氮配体以赋予对Mn2 +的亲和力,但是如何排除其他软阳离子仍然是个谜。通过在体外使代表性的yybP-ykoY核糖开关经受各种阳离子的作用,我们现在发现这些RNA表现出有限的过渡金属离子选择性。在测试的阳离子中,Cd2 +和Mn2 +结合最紧密,三种新的与Cd2 +结合的晶体结构的比较和比较表明,这些核糖开关通过在较软的位点实施七配位(受高自旋Cd2 +和Mn2 +的作用,但不常见)来实现选择性。值得注意的是,Cd2 +和Mn2 +选择性细菌转录因子MntR还使用双核位点内的七配位来实现选择性。
更新日期:2018-08-17
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