Structural basis of the mercury(II)-mediated conformational switching of the dual-function transcriptional regulator MerR.
Structural basis of the mercury(II)-mediated conformational switching of the dual-function transcriptional regulator MerR.
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DOI：
10.1093/nar/gkv681
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发表时间：
2015-09-03
影响因子：
14.9
通讯作者：
Chan NL
中科院分区：
文献类型：
--
作者：
Chang CC;Lin LY;Zou XW;Huang CC;Chan NL
分子操纵子通过编码参与感知、转运和解毒的蛋白质，使细菌对无机汞(Hg2+)和有机汞产生抵抗力。Mer操纵子的表达受到双功能转录调控因子MerR的严格调控。不含金属的apo MerR作为抑制物与Mer操纵子/启动子区域结合，阻止转录启动，但在Hg2+结合时转换为激活剂。为了了解MerR如何与Hg2+相互作用以及Hg2+结合如何调节MerR的功能，我们报道了巨大芽孢杆菌apo和Hg2+结合的MerR的晶体结构，分别对应于MerR的抑制子和激活子构象。据我们所知，apo-merr结构代表了Merr家族成员在其完整和无诱导剂的形式下的第一次可视化。而Hg2+-MERR结构提供了金属蛋白中三配位Hg2+-硫代中心的第一视图，证实MERR通过三角平面配位几何与Hg2+结合。结构比较表明，MerR的构象转变与埋藏的Hg2+结合部位的组装/拆解相耦合，从而为Hg2+介导的MerR的功能转换提供了结构基础。Hg2+诱导的MerR DNA结合域的重新定位表明了一种合理的机制来调控mer操纵子的转录。
The mer operon confers bacterial resistance to inorganic mercury (Hg2+) and organomercurials by encoding proteins involved in sensing, transport and detoxification of these cytotoxic agents. Expression of the mer operon is under tight control by the dual-function transcriptional regulator MerR. The metal-free, apo MerR binds to the mer operator/promoter region as a repressor to block transcription initiation, but is converted into an activator upon Hg2+-binding. To understand how MerR interacts with Hg2+ and how Hg2+-binding modulates MerR function, we report here the crystal structures of apo and Hg2+-bound MerR from Bacillus megaterium, corresponding respectively to the repressor and activator conformation of MerR. To our knowledge, the apo-MerR structure represents the first visualization of a MerR family member in its intact and inducer-free form. And the Hg2+-MerR structure offers the first view of a triligated Hg2+-thiolate center in a metalloprotein, confirming that MerR binds Hg2+ via trigonal planar coordination geometry. Structural comparison revealed the conformational transition of MerR is coupled to the assembly/disassembly of a buried Hg2+ binding site, thereby providing a structural basis for the Hg2+-mediated functional switching of MerR. The pronounced Hg2+-induced repositioning of the MerR DNA-binding domains suggests a plausible mechanism for the transcriptional regulation of the mer operon.