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Structure. 2017 Jul 5;25(7):988-996.e3. doi: 10.1016/j.str.2017.05.004. Epub 2017 Jun 1.

Structural and Dynamics Characterization of the MerR Family Metalloregulator CueR in its Repression and Activation States.

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The Chemistry Department, Faculty of Exact Sciences, Bar Ilan University, Ramat-Gan 5290002, Israel.
Department of Biochemistry and Molecular Biochemistry, George S. Wise Faculty of Life sciences, Tel Aviv University, Ramat Aviv 69978, Israel.
The Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat-Gan 5290002, Israel.
The Chemistry Department, Faculty of Exact Sciences, Bar Ilan University, Ramat-Gan 5290002, Israel. Electronic address:


CueR (Cu export regulator) is a metalloregulator protein that "senses" Cu(I) ions with very high affinity, thereby stimulating DNA binding and the transcription activation of two other metalloregulator proteins. The crystal structures of CueR when unbound or bound to DNA and a metal ion are very similar to each other, and the role of CueR and Cu(I) in initiating the transcription has not been fully understood yet. Using double electron-electron resonance (DEER) measurements and structure modeling, we investigate the conformational changes that CueR undergoes upon binding Cu(I) and DNA in solution. We observe three distinct conformations, corresponding to apo-CueR, DNA-bound CueR in the absence of Cu(I) (the "repression" state), and CueR-Cu(I)-DNA (the "activation" state). We propose a detailed structural mechanism underlying CueR's regulation of the transcription process. The mechanism explicitly shows the dependence of CueR activity on copper, thereby revealing the important negative feedback mechanism essential for regulating the intracellular copper concentration.


ConTemplate; CueR; DEER; EPR; MerR family metalloregulators; protein dynamics; protein-DNA interaction; site-directed spin labeling

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