Structure and Conformational Dynamics of the Metalloregulator MerR upon Binding of Hg(II)
- ORNL
- UGA
The bacterial metalloregulator MerR is the index case of an eponymous family of regulatory proteins, which controls the transcription of a set of genes (the mer operon) conferring mercury resistance in many bacteria. Homodimeric MerR represses transcription in the absence of mercury and activates transcription upon Hg(II) binding. Here, the average structures of the apo and Hg(II)-bound forms of MerR in aqueous solution are examined using small-angle X-ray scattering, indicating an extended conformation of the metal-bound protein and revealing the existence of a novel compact conformation in the absence of Hg(II). Molecular dynamics (MD) simulations are performed to characterize the conformational dynamics of the Hg(II)-bound form. In both small-angle X-ray scattering and MD, the average torsional angle between DNA-binding domains is not, vert, similar 65 . Furthermore, in MD, interdomain motions on a timescale of not, vert, similar 10 ns involving large-amplitude (not, vert, similar 20 ) domain opening-and-closing, coupled to not, vert, similar 40 variations of interdomain torsional angle, are revealed. This correlated domain motion may propagate allosteric changes from the metal-binding site to the DNA-binding site while maintaining DNA contacts required to initiate DNA underwinding.
- Research Organization:
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Oak Ridge Leadership Computing Facility (OLCF); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). National Center for Computational Sciences (NCCS); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Center for Structural Molecular Biology (CSMB)
- Sponsoring Organization:
- USDOE Office of Science (SC)
- DOE Contract Number:
- DE-AC05-00OR22725
- OSTI ID:
- 979335
- Journal Information:
- Journal of Molecular Biology, Vol. 398, Issue 4; ISSN 0022-2836
- Country of Publication:
- United States
- Language:
- English
Similar Records
Transcriptional switching by the metalloregulatory MerR protein: Initial characterization of DNA and mercury(II) binding activities
Molecular structure and dynamics in bacterial mercury resistance