Bacterial riboswitches cooperatively bind Ni(2+) or Co(2+) ions and control expression of heavy metal transporters.
Bacterial riboswitches cooperatively bind Ni(2+) or Co(2+) ions and control expression of heavy metal transporters.
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DOI：
10.1016/j.molcel.2015.02.009
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发表时间：
2015-03-19
期刊：
影响因子：
16
通讯作者：
Breaker RR
中科院分区：
文献类型：
--
作者：
Furukawa K;Ramesh A;Zhou Z;Weinberg Z;Vallery T;Winkler WC;Breaker RR
细菌经常会遇到周围环境中不同浓度的金属。当金属耗尽，或者相反，产生毒性时，微生物将激活细胞反应，以维持金属稳态。一套金属感应调节（“金属调节”）蛋白通过变构耦合目标金属的选择性结合与 DNA 结合域的活性来协调这些反应。然而，我们在此报告了一类广泛存在的核糖开关 RNA 的发现、验证和结构细节，其成员选择性且紧密地结合低丰度过渡金属 Ni2+ 和 Co2+。这些核糖开关协同结合金属，并具有低微摩尔范围的亲和力。 Co2+ 结合 RNA 的结构揭示了分子接触网络，解释了它如何实现相邻位点之间的协同结合。这些发现表明，除了金属调节蛋白之外，细菌已经进化到利用高度选择性的金属调节核糖开关来检测和响应重金属的毒性水平。
Bacteria regularly encounter widely varying metal concentrations in their surrounding environment. As metals become depleted, or, conversely, accrue to toxicity, microbes will activate cellular responses that act to maintain metal homeostasis. A suite of metal-sensing regulatory (‘metalloregulatory’) proteins orchestrate these responses by allosterically coupling the selective binding of target metals to the activity of DNA-binding domains. However, we report here the discovery, validation and structural details of a widespread class of riboswitch RNAs, whose members selectively and tightly bind the low abundance transition metals, Ni2+ and Co2+. These riboswitches bind metal cooperatively, and with affinities in the low micromolar range. The structure of a Co2+-bound RNA reveals a network of molecular contacts that explain how it achieves cooperative binding between adjacent sites. These findings reveal that bacteria have evolved to utilize highly selective metalloregulatory riboswitches, in addition to metalloregulatory proteins, for detecting and responding to toxic levels of heavy metals.