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

Science. 2003 Sep 5;301(5638):1383-7. doi: 10.1126/science.1085950.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Binding Sites
  • Copper / metabolism*
  • Crystallization
  • Crystallography, X-Ray
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Dimerization
  • Escherichia coli / chemistry*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Helix-Turn-Helix Motifs
  • Hydrogen Bonding
  • Hydrophobic and Hydrophilic Interactions
  • Ligands
  • Metals / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Oxidation-Reduction
  • Promoter Regions, Genetic
  • Protein Conformation
  • Protein Structure, Secondary
  • Sequence Alignment
  • Thermodynamics
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • Zinc / metabolism

Substances

  • Bacterial Proteins
  • DNA-Binding Proteins
  • Escherichia coli Proteins
  • Ligands
  • MerR protein, Bacteria
  • Metals
  • Transcription Factors
  • ZntR protein, E coli
  • ZntR protein, bacteria
  • Copper
  • Zinc

Associated data

  • PDB/1Q05
  • PDB/1Q06
  • PDB/1Q07
  • PDB/1Q08
  • PDB/1Q09
  • PDB/1Q0A