Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 5 September 2003:
Vol. 301. no. 5638, pp. 1383 - 1387
DOI: 10.1126/science.1085950
Prev | Table of Contents | Next

Reports

Molecular Basis of Metal-Ion Selectivity and Zeptomolar Sensitivity by CueR

Anita Changela,1* Kui Chen,2* Yi Xue,2 Jackie Holschen,2 Caryn E. Outten,2 Thomas V. O'Halloran,1,2{dagger} Alfonso Mondragón1{dagger}

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.

1 Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, 2205Tech Drive, Evanston, IL 60208, USA.
2 Department of Chemistry, Northwestern University, 2205Tech Drive, Evanston, IL 60208, USA.



* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: t-ohalloran{at}northwestern.edu (T.V.O.) and a-mondragon{at}northwestern.edu (A.M.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Metal Homeostasis Protein, Lsp, of Streptococcus pyogenes Is Necessary for Acquisition of Zinc and Virulence.
B. F. Weston, A. Brenot, and M. G. Caparon (2009)
Infect. Immun. 77, 2840-2848
   Abstract »    Full Text »    PDF »
An Intact Urease Assembly Pathway Is Required To Compete with NikR for Nickel Ions in Helicobacter pylori.
E. L. Benanti and P. T. Chivers (2009)
J. Bacteriol. 191, 2405-2408
   Abstract »    Full Text »    PDF »
Adaptation of Aerobically Growing Pseudomonas aeruginosa to Copper Starvation.
E. Frangipani, V. I. Slaveykova, C. Reimmann, and D. Haas (2008)
J. Bacteriol. 190, 6706-6717
   Abstract »    Full Text »    PDF »
Complete Loss of Post-translational Modifications Triggers Fibrillar Aggregation of SOD1 in the Familial Form of Amyotrophic Lateral Sclerosis.
Y. Furukawa, K. Kaneko, K. Yamanaka, T. V. O'Halloran, and N. Nukina (2008)
J. Biol. Chem. 283, 24167-24176
   Abstract »    Full Text »    PDF »
Glutathione and Transition-Metal Homeostasis in Escherichia coli.
K. Helbig, C. Bleuel, G. J. Krauss, and D. H. Nies (2008)
J. Bacteriol. 190, 5431-5438
   Abstract »    Full Text »    PDF »
Copper sensing function of Drosophila metal-responsive transcription factor-1 is mediated by a tetranuclear Cu(I) cluster.
X. Chen, H. Hua, K. Balamurugan, X. Kong, L. Zhang, G. N. George, O. Georgiev, W. Schaffner, and D. P. Giedroc (2008)
Nucleic Acids Res. 36, 3128-3138
   Abstract »    Full Text »    PDF »
Mechanism of Cu+-transporting ATPases: Soluble Cu+ chaperones directly transfer Cu+ to transmembrane transport sites.
M. Gonzalez-Guerrero and J. M. Arguello (2008)
PNAS 105, 5992-5997
   Abstract »    Full Text »    PDF »
Crystal structure of the [2Fe-2S] oxidative-stress sensor SoxR bound to DNA.
S. Watanabe, A. Kita, K. Kobayashi, and K. Miki (2008)
PNAS 105, 4121-4126
   Abstract »    Full Text »    PDF »
DNA binding shifts the redox potential of the transcription factor SoxR.
A. A. Gorodetsky, L. E. P. Dietrich, P. E. Lee, B. Demple, D. K. Newman, and J. K. Barton (2008)
PNAS 105, 3684-3689
   Abstract »    Full Text »    PDF »
SufR Coordinates Two [4Fe-4S]2+, 1+ Clusters and Functions as a Transcriptional Repressor of the sufBCDS Operon and an Autoregulator of sufR in Cyanobacteria.
G. Shen, R. Balasubramanian, T. Wang, Y. Wu, L. M. Hoffart, C. Krebs, D. A. Bryant, and J. H. Golbeck (2007)
J. Biol. Chem. 282, 31909-31919
   Abstract »    Full Text »    PDF »
NMR Structural Analysis of Cadmium Sensing by Winged Helix Repressor CmtR.
L. Banci, I. Bertini, F. Cantini, S. Ciofi-Baffoni, J. S. Cavet, C. Dennison, A. I. Graham, D. R. Harvie, and N. J. Robinson (2007)
J. Biol. Chem. 282, 30181-30188
   Abstract »    Full Text »    PDF »
Ligand-Controlled Proteolysis of the Escherichia coli Transcriptional Regulator ZntR.
M. Pruteanu, S. B. Neher, and T. A. Baker (2007)
J. Bacteriol. 189, 3017-3025
   Abstract »    Full Text »    PDF »
A Galvanizing Story--Protein Stability and Zinc Homeostasis.
P. T. Chivers (2007)
J. Bacteriol. 189, 2953-2954
   Full Text »    PDF »
Characterization of the Cytochrome c Oxidase Assembly Factor Cox19 of Saccharomyces cerevisiae.
K. Rigby, L. Zhang, P. A. Cobine, G. N. George, and D. R. Winge (2007)
J. Biol. Chem. 282, 10233-10242
   Abstract »    Full Text »    PDF »
Functional Analysis of the Carboxy-Terminal Region of Bacillus subtilis TnrA, a MerR Family Protein.
L. V. Wray Jr. and S. H. Fisher (2007)
J. Bacteriol. 189, 20-27
   Abstract »    Full Text »    PDF »
The delivery of copper for thylakoid import observed by NMR.
L. Banci, I. Bertini, S. Ciofi-Baffoni, N. G. Kandias, N. J. Robinson, G. A. Spyroulias, X.-C. Su, S. Tottey, and M. Vanarotti (2006)
PNAS 103, 8320-8325
   Abstract »    Full Text »    PDF »
Cross-Regulation of the Bacillus subtilis glnRA and tnrA Genes Provides Evidence for DNA Binding Site Discrimination by GlnR and TnrA..
J. M. Zalieckas, L. V. Wray Jr., and S. H. Fisher (2006)
J. Bacteriol. 188, 2578-2585
   Abstract »    Full Text »    PDF »
Hg(II) sequestration and protection by the MerR metal-binding domain (MBD)..
J. Qin, L. Song, H. Brim, M. J. Daly, and A. O. Summers (2006)
Microbiology 152, 709-719
   Abstract »    Full Text »    PDF »
The clpB gene of Bifidobacterium breve UCC 2003: transcriptional analysis and first insights into stress induction.
M. Ventura, J. G. Kenny, Z. Zhang, G. F. Fitzgerald, and D. van Sinderen (2005)
Microbiology 151, 2861-2872
   Abstract »    Full Text »    PDF »
Constitutive soxR Mutations Contribute to Multiple-Antibiotic Resistance in Clinical Escherichia coli Isolates.
A. Koutsolioutsou, S. Pena-Llopis, and B. Demple (2005)
Antimicrob. Agents Chemother. 49, 2746-2752
   Abstract »    Full Text »    PDF »
Role of the Extracytoplasmic Function Protein Family Sigma Factor RpoE in Metal Resistance of Escherichia coli.
M. Egler, C. Grosse, G. Grass, and D. H. Nies (2005)
J. Bacteriol. 187, 2297-2307
   Abstract »    Full Text »    PDF »
The bldC Developmental Locus of Streptomyces coelicolor Encodes a Member of a Family of Small DNA-Binding Proteins Related to the DNA-Binding Domains of the MerR Family.
A. C. Hunt, L. Servin-Gonzalez, G. H. Kelemen, and M. J. Buttner (2005)
J. Bacteriol. 187, 716-728
   Abstract »    Full Text »    PDF »
The Serratia gene cluster encoding biosynthesis of the red antibiotic, prodigiosin, shows species- and strain-dependent genome context variation.
A. K. P. Harris, N. R. Williamson, H. Slater, A. Cox, S. Abbasi, I. Foulds, H. T. Simonsen, F. J. Leeper, and G. P. C. Salmond (2004)
Microbiology 150, 3547-3560
   Abstract »    Full Text »    PDF »
Functional Analysis of SoxR Residues Affecting Transduction of Oxidative Stress Signals into Gene Expression.
M. Chander and B. Demple (2004)
J. Biol. Chem. 279, 41603-41610
   Abstract »    Full Text »    PDF »
The N Terminus of Myxococcus xanthus CarA Repressor Is an Autonomously Folding Domain That Mediates Physical and Functional Interactions with Both Operator DNA and Antirepressor Protein.
M. C. Perez-Marin, J. J. Lopez-Rubio, F. J. Murillo, M. Elias-Arnanz, and S. Padmanabhan (2004)
J. Biol. Chem. 279, 33093-33103
   Abstract »    Full Text »    PDF »
Splicing Factor hSlu7 Contains a Unique Functional Domain Required to Retain the Protein within the Nucleus.
N. Shomron, M. Reznik, and G. Ast (2004)
Mol. Biol. Cell 15, 3782-3795
   Abstract »    Full Text »    PDF »
Solution Structures of a Cyanobacterial Metallochaperone: INSIGHT INTO AN ATYPICAL COPPER-BINDING MOTIF.
L. Banci, I. Bertini, S. Ciofi-Baffoni, X.-C. Su, G. P. M. Borrelly, and N. J. Robinson (2004)
J. Biol. Chem. 279, 27502-27510
   Abstract »    Full Text »    PDF »
The Structural Mechanism for Transcription Activation by MerR Family Member Multidrug Transporter Activation, N Terminus.
K. J. Newberry and R. G. Brennan (2004)
J. Biol. Chem. 279, 20356-20362
   Abstract »    Full Text »    PDF »
A Novel Cyanobacterial SmtB/ArsR Family Repressor Regulates the Expression of a CPx-ATPase and a Metallothionein in Response to Both Cu(I)/Ag(I) and Zn(II)/Cd(II).
T. Liu, S. Nakashima, K. Hirose, M. Shibasaka, M. Katsuhara, B. Ezaki, D. P. Giedroc, and K. Kasamo (2004)
J. Biol. Chem. 279, 17810-17818
   Abstract »    Full Text »    PDF »
Engineered Single-Chain, Antiparallel, Coiled Coil Mimics the MerR Metal Binding Site.
L. Song, J. Caguiat, Z. Li, J. Shokes, R. A. Scott, L. Olliff, and A. O. Summers (2004)
J. Bacteriol. 186, 1861-1868
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)