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.
Transition Metal Speciation in the Cell: Insights from the Chemistry of Metal Ion Receptors
Lydia A. Finney1 and
Thomas V. O'Halloran1,2*
The essential transition metal ions are avidly accumulated bycells, yet they have two faces: They are put to use as requiredcofactors, but they also can catalyze cytotoxic reactions. Severalfamilies of proteins are emerging that control the activityof intracellular metal ions and help confine them to vital roles.These include integral transmembrane transporters, metalloregulatorysensors, and diffusible cytoplasmic metallochaperone proteinsthat protect and guide metal ions to targets. It is becomingclear that many of these proteins use atypical coordinationchemistry to accomplish their unique goals. The different coordinationnumbers, types of coordinating residues, and solvent accessibilitiesof these sites are providing insight into the inorganic chemistryof the cytoplasm.
1 Department of Chemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 602083113, USA. 2 Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 602083113, USA.
* To whom correspondence should be addressed at the Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL 602083113, USA.
The editors suggest the following Related Resources on Science sites:
In Science Magazine
NEWS
Jocelyn Kaiser (21 May 2003) Science300 (5621), 926.
[DOI: 10.1126/science.300.5621.926] |Summary »|Full Text »|PDF »
INTRODUCTION TO SPECIAL ISSUE
Caroline Ash and Richard Stone (9 May 2003) Science300 (5621), 925.
[DOI: 10.1126/science.300.5621.925] |Summary »|PDF »
NEWS
Jocelyn Kaiser (9 May 2003) Science300 (5621), 927.
[DOI: 10.1126/science.300.5621.927] |Summary »|Full Text »|PDF »
REVIEW
Douglas C. Rees and James B. Howard (9 May 2003) Science300 (5621), 929.
[DOI: 10.1126/science.1083075] |Abstract »|Full Text »|PDF »
REVIEW
Katherine H. Thompson and Chris Orvig (9 May 2003) Science300 (5621), 936.
[DOI: 10.1126/science.1083004] |Abstract »|Full Text »|PDF »
REVIEW
F. M. M. Morel and N. M. Price (9 May 2003) Science300 (5621), 944.
[DOI: 10.1126/science.1083545] |Abstract »|Full Text »|PDF »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Copper Delivery by the Copper Chaperone for Chloroplast and Cytosolic Copper/Zinc-Superoxide Dismutases: Regulation and Unexpected Phenotypes in an Arabidopsis Mutant.
C. M. Cohu, S. E. Abdel-Ghany, K. A. Gogolin Reynolds, A. M. Onofrio, J. R. Bodecker, J. A. Kimbrel, K. K. Niyogi, and M. Pilon (2009)
Mol Plant
|Abstract »|Full Text »|PDF »
The Linker Region in Receptor Guanylyl Cyclases Is a Key Regulatory Module: MUTATIONAL ANALYSIS OF GUANYLYL CYCLASE C.
S. Saha, K. H. Biswas, C. Kondapalli, N. Isloor, and S. S. Visweswariah (2009)
J. Biol. Chem.
284, 27135-27145
|Abstract »|Full Text »|PDF »
Functional and Expression Analyses of the cop Operon, Required for Copper Resistance in Agrobacterium tumefaciens.
S. Nawapan, N. Charoenlap, A. Charoenwuttitam, P. Saenkham, S. Mongkolsuk, and P. Vattanaviboon (2009)
J. Bacteriol.
191, 5159-5168
|Abstract »|Full Text »|PDF »
The Mechanism of Iron Homeostasis in the Unicellular Cyanobacterium Synechocystis sp. PCC 6803 and Its Relationship to Oxidative Stress.
S. Shcolnick, T. C. Summerfield, L. Reytman, L. A. Sherman, and N. Keren (2009)
Plant Physiology
150, 2045-2056
|Abstract »|Full Text »|PDF »
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 »
Growth Phase and Metal-Dependent Transcriptional Regulation of the fecA Genes in Helicobacter pylori.
A. Danielli, S. Romagnoli, D. Roncarati, L. Costantino, I. Delany, and V. Scarlato (2009)
J. Bacteriol.
191, 3717-3725
|Abstract »|Full Text »|PDF »
A P-type ATPase importer that discriminates between essential and toxic transition metals.
ATM-mediated Transcriptional Elevation of Prion in Response to Copper-induced Oxidative Stress.
K. Qin, L. Zhao, R. D. Ash, W. F. McDonough, and R. Y. Zhao (2009)
J. Biol. Chem.
284, 4582-4593
|Abstract »|Full Text »|PDF »
Knock down of Caenorhabditis elegans cutc-1 Exacerbates the Sensitivity Toward High Levels of Copper.
S. Calafato, S. Swain, S. Hughes, P. Kille, and S. R. Sturzenbaum (2008)
Toxicol. Sci.
106, 384-391
|Abstract »|Full Text »|PDF »
Structural explanation for the role of Mn2+ in the activity of {phi}6 RNA-dependent RNA polymerase.
M. M. Poranen, P. S. Salgado, M. R. L. Koivunen, S. Wright, D. H. Bamford, D. I. Stuart, and J. M. Grimes (2008)
Nucleic Acids Res.
36, 6633-6644
|Abstract »|Full Text »|PDF »
A Plasma Membrane-associated Protein of Arabidopsis thaliana AtPCaP1 Binds Copper Ions and Changes Its Higher Order Structure.
N. Nagasaki-Takeuchi, M. Miyano, and M. Maeshima (2008)
J. Biochem.
144, 487-497
|Abstract »|Full Text »|PDF »
Opposite Effects of Mn2+ and Zn2+ on PsaR-Mediated Expression of the Virulence Genes pcpA, prtA, and psaBCA of Streptococcus pneumoniae.
T. G. Kloosterman, R. M. Witwicki, M. M. van der Kooi-Pol, J. J. E. Bijlsma, and O. P. Kuipers (2008)
J. Bacteriol.
190, 5382-5393
|Abstract »|Full Text »|PDF »
The Bradyrhizobium japonicum Irr Protein Is a Transcriptional Repressor with High-Affinity DNA-Binding Activity.
I. Sangwan, S. K. Small, and M. R. O'Brian (2008)
J. Bacteriol.
190, 5172-5177
|Abstract »|Full Text »|PDF »
His-tags as Zn(II) binding motifs in a protein-based fluorescent sensor.
T. H. Evers, M. A.M. Appelhof, E.W. Meijer, and M. Merkx (2008)
Protein Eng. Des. Sel.
21, 529-536
|Abstract »|Full Text »|PDF »
Mitochondrial copper(I) transfer from Cox17 to Sco1 is coupled to electron transfer.
L. Banci, I. Bertini, S. Ciofi-Baffoni, T. Hadjiloi, M. Martinelli, and P. Palumaa (2008)
PNAS
105, 6803-6808
|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 »
Non-transferrin-bound iron reaches mitochondria by a chelator-inaccessible mechanism: biological and clinical implications.
M. Shvartsman, R. Kikkeri, A. Shanzer, and Z. I. Cabantchik (2007)
Am J Physiol Cell Physiol
293, C1383-C1394
|Abstract »|Full Text »|PDF »
The Metalloreductase Fre6p in Fe-Efflux from the Yeast Vacuole.
A. Singh, N. Kaur, and D. J. Kosman (2007)
J. Biol. Chem.
282, 28619-28626
|Abstract »|Full Text »|PDF »
Differential Expression of the Three Multicopper Oxidases from Myxococcus xanthus.
M. C. Sanchez-Sutil, N. Gomez-Santos, A. Moraleda-Munoz, L. O. Martins, J. Perez, and J. Munoz-Dorado (2007)
J. Bacteriol.
189, 4887-4898
|Abstract »|Full Text »|PDF »
Crystal Structure and Function of the Zinc Uptake Regulator FurB from Mycobacterium tuberculosis.
D. Lucarelli, S. Russo, E. Garman, A. Milano, W. Meyer-Klaucke, and E. Pohl (2007)
J. Biol. Chem.
282, 9914-9922
|Abstract »|Full Text »|PDF »
X-ray fluorescence microscopy reveals large-scale relocalization and extracellular translocation of cellular copper during angiogenesis.
L. Finney, S. Mandava, L. Ursos, W. Zhang, D. Rodi, S. Vogt, D. Legnini, J. Maser, F. Ikpatt, O. I. Olopade, et al. (2007)
PNAS
104, 2247-2252
|Abstract »|Full Text »|PDF »
An arsenic metallochaperone for an arsenic detoxification pump.
Survival and Growth in the Presence of Elevated Copper: Transcriptional Profiling of Copper-Stressed Pseudomonas aeruginosa..
G. M. Teitzel, A. Geddie, S. K. De Long, M. J. Kirisits, M. Whiteley, and M. R. Parsek (2006)
J. Bacteriol.
188, 7242-7256
|Abstract »|Full Text »|PDF »
Bioactive Properties of Iron-Containing Carbon Monoxide-Releasing Molecules.
P. Sawle, J. Hammad, I. J. S. Fairlamb, B. Moulton, C. T. O'Brien, J. M. Lynam, A. K. Duhme-Klair, R. Foresti, and R. Motterlini (2006)
J. Pharmacol. Exp. Ther.
318, 403-410
|Abstract »|Full Text »|PDF »
A systems view of haloarchaeal strategies to withstand stress from transition metals.
A. Kaur, M. Pan, M. Meislin, M. T. Facciotti, R. El-Gewely, and N. S. Baliga (2006)
Genome Res.
16, 841-854
|Abstract »|Full Text »|PDF »
Influence of Location of a Fluorescent Zinc Probe in Brain Slices on Its Response to Synaptic Activation.
An Architectural Framework That May Lie at the Core of the Postsynaptic Density.
M. K. Baron, T. M. Boeckers, B. Vaida, S. Faham, M. Gingery, M. R. Sawaya, D. Salyer, E. D. Gundelfinger, and J. U. Bowie (2006)
Science
311, 531-535
|Abstract »|Full Text »|PDF »
The Role of Metallothionein in the Pathogenesis of Acute Lung Injury.
S. C. Wesselkamper, S. A. McDowell, M. Medvedovic, T. P. Dalton, H. S. Deshmukh, M. A. Sartor, L. M. Case, L. N. Henning, M. T. Borchers, C. R. Tomlinson, et al. (2006)
Am. J. Respir. Cell Mol. Biol.
34, 73-82
|Abstract »|Full Text »|PDF »
Mechanism of metal ion activation of the diphtheria toxin repressor DtxR.
J. A. D'Aquino, J. Tetenbaum-Novatt, A. White, F. Berkovitch, and D. Ringe (2005)
PNAS
102, 18408-18413
|Abstract »|Full Text »|PDF »
Nitric Oxide and Zinc Homeostasis in Acute Lung Injury.
C. M. St. Croix, K. Leelavaninchkul, S. C. Watkins, V. E. Kagan, and B. R. Pitt (2005)
Proceedings of the ATS
2, 236-242
|Abstract »|Full Text »|PDF »
Rv2358 and FurB: Two Transcriptional Regulators from Mycobacterium tuberculosis Which Respond to Zinc.
F. Canneva, M. Branzoni, G. Riccardi, R. Provvedi, and A. Milano (2005)
J. Bacteriol.
187, 5837-5840
|Abstract »|Full Text »|PDF »
Prediction of water and metal binding sites and their affinities by using the Fold-X force field.
J. W. H. Schymkowitz, F. Rousseau, I. C. Martins, J. Ferkinghoff-Borg, F. Stricher, and L. Serrano (2005)
PNAS
102, 10147-10152
|Abstract »|Full Text »|PDF »
PrpZ, a Salmonella enterica serovar Typhi serine/threonine protein phosphatase 2C with dual substrate specificity.
A copper(I) protein possibly involved in the assembly of CuA center of bacterial cytochrome c oxidase.
L. Banci, I. Bertini, S. Ciofi-Baffoni, E. Katsari, N. Katsaros, K. Kubicek, and S. Mangani (2005)
PNAS
102, 3994-3999
|Abstract »|Full Text »|PDF »
Regulation of Resistance to Copper in Xanthomonas axonopodis pv. vesicatoria.
A. E. Voloudakis, T. M. Reignier, and D. A. Cooksey (2005)
Appl. Envir. Microbiol.
71, 782-789
|Abstract »|Full Text »|PDF »
The crystal structure of yeast copper thionein: The solution of a long-lasting enigma.
V. Calderone, B. Dolderer, H.-J. Hartmann, H. Echner, C. Luchinat, C. Del Bianco, S. Mangani, and U. Weser (2005)
PNAS
102, 51-56
|Abstract »|Full Text »|PDF »
Mobilization of Intracellular Copper Stores by the Ctr2 Vacuolar Copper Transporter.
E. M. Rees, J. Lee, and D. J. Thiele (2004)
J. Biol. Chem.
279, 54221-54229
|Abstract »|Full Text »|PDF »
Cuprous Oxidase Activity of CueO from Escherichia coli.
S. K. Singh, G. Grass, C. Rensing, and W. R. Montfort (2004)
J. Bacteriol.
186, 7815-7817
|Abstract »|Full Text »|PDF »
Insights into the Mechanism of 3-Deoxy-D-arabino-heptulosonate 7-Phosphate Synthase (Phe) from Escherichia coli Using a Transient Kinetic Analysis.
C. Furdui, L. Zhou, R. W. Woodard, and K. S. Anderson (2004)
J. Biol. Chem.
279, 45618-45625
|Abstract »|Full Text »|PDF »
Methanobactin, a Copper-Acquisition Compound from Methane-Oxidizing Bacteria.
H. J. Kim, D. W. Graham, A. A. DiSpirito, M. A. Alterman, N. Galeva, C. K. Larive, D. Asunskis, and P. M. A. Sherwood (2004)
Science
305, 1612-1615
|Abstract »|Full Text »|PDF »
Copper Ions Stimulate Polyphosphate Degradation and Phosphate Efflux in Acidithiobacillus ferrooxidans.
Linkage between Catecholate Siderophores and the Multicopper Oxidase CueO in Escherichia coli.
G. Grass, K. Thakali, P. E. Klebba, D. Thieme, A. Muller, G. F. Wildner, and C. Rensing (2004)
J. Bacteriol.
186, 5826-5833
|Abstract »|Full Text »|PDF »
Critical Roles of Bacterioferritins in Iron Storage and Proliferation of Cyanobacteria.
N. Keren, R. Aurora, and H. B. Pakrasi (2004)
Plant Physiology
135, 1666-1673
|Abstract »|Full Text »|PDF »
Thermodynamic Studies of the Mechanism of Metal Binding to the Escherichia coli Zinc Transporter YiiP.
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 »
Yeast Contain a Non-proteinaceous Pool of Copper in the Mitochondrial Matrix.
P. A. Cobine, L. D. Ojeda, K. M. Rigby, and D. R. Winge (2004)
J. Biol. Chem.
279, 14447-14455
|Abstract »|Full Text »|PDF »
An Engineered Pathway for the Formation of Protein Disulfide Bonds.
L. Masip, J. L. Pan, S. Haldar, J. E. Penner-Hahn, M. P. DeLisa, G. Georgiou, J. C. A. Bardwell, and J.-F. Collet (2004)
Science
303, 1185-1189
|Abstract »|Full Text »|PDF »
From the Cover: A tautomeric zinc sensor for ratiometric fluorescence imaging: Application to nitric oxide-induced release of intracellular zinc.
C. J. Chang, J. Jaworski, E. M. Nolan, M. Sheng, and S. J. Lippard (2004)
PNAS
101, 1129-1134
|Abstract »|Full Text »|PDF »
The Stable Isotope Geochemistry of Copper and Zinc.
F. Albarede (2004)
Reviews in Mineralogy and Geochemistry
55, 409-427
|Full Text »|PDF »
The non-classical export routes: FGF1 and IL-1{alpha} point the way.
I. Prudovsky, A. Mandinova, R. Soldi, C. Bagala, I. Graziani, M. Landriscina, F. Tarantini, M. Duarte, S. Bellum, H. Doherty, et al. (2003)
J. Cell Sci.
116, 4871-4881
|Abstract »|Full Text »|PDF »
Structural Basis for the Function of the N-terminal Domain of the ATPase CopA from Bacillus subtilis.
L. Banci, I. Bertini, S. Ciofi-Baffoni, L. Gonnelli, and X.-C. Su (2003)
J. Biol. Chem.
278, 50506-50513
|Abstract »|Full Text »|PDF »
Two MerR homologues that affect copper induction of the Bacillus subtilis copZA operon.
Production of High-Quality Particulate Methane Monooxygenase in High Yields from Methylococcus capsulatus (Bath) with a Hollow-Fiber Membrane Bioreactor.
S. S.-F. Yu, K. H.-C. Chen, M. Y.-H. Tseng, Y.-S. Wang, C.-F. Tseng, Y.-J. Chen, D.-S. Huang, and S. I. Chan (2003)
J. Bacteriol.
185, 5915-5924
|Abstract »|Full Text »|PDF »
Molecular Basis of Metal-Ion Selectivity and Zeptomolar Sensitivity by CueR.
A. Changela, K. Chen, Y. Xue, J. Holschen, C. E. Outten, T. V. O'Halloran, and A. Mondragon (2003)
Science
301, 1383-1387
|Abstract »|Full Text »|PDF »