Molecular basis of metal-ion selectivity and zeptomolar sensitivity by CueR.
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.
Changela
Anita
A
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, 2205Tech Drive, Evanston, IL 60208, USA.
Chen
Kui
K
Xue
Yi
Y
Holschen
Jackie
J
Outten
Caryn E
CE
O'Halloran
Thomas V
TV
Mondragón
Alfonso
A
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D003300:Copper / Q000378:metabolism*; D003460:Crystallization; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D004926:Escherichia coli / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019077:Helix-Turn-Helix Motifs; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008670:Metals / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D013816:Thermodynamics; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D015032:Zinc / Q000378:metabolism
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D008024:Ligands; C051124:MerR protein, Bacteria; D008670:Metals; D014157:Transcription Factors; C492246:ZntR protein, E coli; C118628:ZntR protein, bacteria; D003300:Copper; D015032:Zinc