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

Hila Sameach, Aya Narunsky, Salome Azoulay-Ginsburg, Lada Gevorkyan-Aiapetov, Yonathan Zehavi, Yoni Moskovitz, Tamar Juven-Gershon, Nir Ben-Tal, Sharon Ruthstein

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)988-996.e3
JournalStructure
Volume25
Issue number7
DOIs
StatePublished - 5 Jul 2017

Keywords

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

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