Structural basis of the mercury(II)-mediated conformational switching of the dual-function transcriptional regulator MerR.

Abstract

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.