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

doi:10.1126/science.1085950

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 journal › Article › peer-review

549 Scopus citations

Abstract

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 language	English (US)
Pages (from-to)	1383-1387
Number of pages	5
Journal	Science
Volume	301
Issue number	5638
DOIs	https://doi.org/10.1126/science.1085950
State	Published - Sep 5 2003

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title = "Molecular basis of metal-ion selectivity and zeptomolar sensitivity by CueR",

abstract = "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.",

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T1 - Molecular basis of metal-ion selectivity and zeptomolar sensitivity by CueR

AU - Changela, Anita

AU - Chen, Kui

AU - Xue, Yi

AU - Holschen, Jackie

AU - Outten, Caryn E.

AU - O'Halloran, Thomas V.

AU - Mondragón, Alfonso

PY - 2003/9/5

Y1 - 2003/9/5

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AB - 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.

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

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Crystal structure of the Zn(II) form of E. coli ZntR, a zinc-sensing transcriptional regulator (space group I4122)

Crystal structure of the Ag(I) form of E. coli CueR, a copper efflux regulator

Crystal structure of the Au(I) form of E. coli CueR, a copper efflux regulator

Cite this

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

Abstract

ASJC Scopus subject areas

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Datasets

Crystal structure of the Zn(II) form of E. coli ZntR, a zinc-sensing transcriptional regulator (space group I4122)

Crystal structure of the Ag(I) form of E. coli CueR, a copper efflux regulator

Crystal structure of the Au(I) form of E. coli CueR, a copper efflux regulator

Cite this