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 +1transition-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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Bacterial Proteins / chemistry*
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism*
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Binding Sites
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Copper / metabolism*
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Crystallization
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Crystallography, X-Ray
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Dimerization
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Escherichia coli / chemistry*
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Escherichia coli / genetics
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Escherichia coli / metabolism
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Escherichia coli Proteins / chemistry*
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Escherichia coli Proteins / genetics
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Escherichia coli Proteins / metabolism*
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Helix-Turn-Helix Motifs
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Hydrogen Bonding
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Hydrophobic and Hydrophilic Interactions
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Ligands
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Metals / metabolism*
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Models, Molecular
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Molecular Sequence Data
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Oxidation-Reduction
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Promoter Regions, Genetic
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Protein Conformation
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Protein Structure, Secondary
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Sequence Alignment
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Thermodynamics
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcriptional Activation
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Zinc / metabolism
Substances
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Bacterial Proteins
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DNA-Binding Proteins
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Escherichia coli Proteins
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Ligands
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MerR protein, Bacteria
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Metals
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Transcription Factors
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ZntR protein, E coli
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ZntR protein, bacteria
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Copper
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Zinc
Associated data
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PDB/1Q05
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PDB/1Q06
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PDB/1Q07
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PDB/1Q08
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PDB/1Q09
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PDB/1Q0A