Furukawa Kazuhiro, Ramesh Arati, Zhou Zhiyuan, Weinberg Zasha, Vallery Tenaya, Winkler Wade C, Breaker Ronald R
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
Mol Cell. 2015 Mar 19;57(6):1088-1098. doi: 10.1016/j.molcel.2015.02.009.
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, Ni(2+) and Co(2+). These riboswitches bind metal cooperatively, and with affinities in the low micromolar range. The structure of a Co(2+)-bound RNA reveals a network of molecular contacts that explains 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.
细菌在其周围环境中经常遇到浓度差异很大的金属。随着金属变得枯竭，或者相反，积累到有毒水平，微生物会激活细胞反应以维持金属稳态。一组金属感应调节（“金属调节”）蛋白通过将靶金属的选择性结合与DNA结合域的活性进行变构偶联来协调这些反应。然而，我们在此报告了一类广泛存在的核糖开关RNA的发现、验证及结构细节，其成员选择性且紧密地结合低丰度的过渡金属镍离子（Ni²⁺）和钴离子（Co²⁺）。这些核糖开关以协同方式结合金属，亲和力在低微摩尔范围内。结合钴离子（Co²⁺）的RNA结构揭示了一个分子接触网络，解释了它如何在相邻位点之间实现协同结合。这些发现表明，除了金属调节蛋白外，细菌已经进化出利用高度选择性的金属调节核糖开关来检测和应对重金属的毒性水平。
