Structural basis of the mercury(II)-mediated conformational switching of the dual-function transcriptional regulator MerR.
Nucleic Acids Res
; 43(15): 7612-23, 2015 Sep 03.
Article
en En
| MEDLINE
| ID: mdl-26150423
ABSTRACT
The mer operon confers bacterial resistance to inorganic mercury (Hg(2+)) 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 Hg(2+)-binding. To understand how MerR interacts with Hg(2+) and how Hg(2+)-binding modulates MerR function, we report here the crystal structures of apo and Hg(2+)-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 Hg(2+)-MerR structure offers the first view of a triligated Hg(2+)-thiolate center in a metalloprotein, confirming that MerR binds Hg(2+) via trigonal planar coordination geometry. Structural comparison revealed the conformational transition of MerR is coupled to the assembly/disassembly of a buried Hg(2+) binding site, thereby providing a structural basis for the Hg(2+)-mediated functional switching of MerR. The pronounced Hg(2+)-induced repositioning of the MerR DNA-binding domains suggests a plausible mechanism for the transcriptional regulation of the mer operon.
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1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
/
Proteínas Bacterianas
/
Transactivadores
/
Proteínas de Unión al ADN
/
Mercurio
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2015
Tipo del documento:
Article
País de afiliación:
Taiwán