Molecular basis of metal-ion selectivity and zeptomolar sensitivity by CueR

Anita Changela, Kui Chen, Yi Xue, Jackie Holschen, Caryn E. Outten, Thomas V. O'Halloran*, Alfonso Mondragón

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

525 Scopus citations


The earliest of a series of copper efflux genes in Escherichia coli are controlled by CueR, a member of the MerR family of transcriptional activators. Thermodynamic calibration of CueR reveals a zeptomolar (10-21 molar) sensitivity to free Cu+, which is far less than one atom per cell. Atomic details of this extraordinary sensitivity and selectivity for +1 transition-metal ions are revealed by comparing the crystal structures of CueR and a Zn2+-sensing homolog, ZntR. An unusual buried metal-receptor site in CueR restricts the metal to a linear, two-coordinate geometry and uses helix-dipole and hydrogen-bonding interactions to enhance metal binding. This binding mode is rare among metalloproteins but well suited for an ultrasensitive genetic switch.

Original languageEnglish (US)
Pages (from-to)1383-1387
Number of pages5
Issue number5638
StatePublished - Sep 5 2003

ASJC Scopus subject areas

  • General


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