Transition Metal Speciation in the Cell: Insights from the Chemistry of Metal Ion Receptors
Abstract
The essential transition metal ions are avidly accumulated by cells, yet they have two faces: They are put to use as required cofactors, but they also can catalyze cytotoxic reactions. Several families of proteins are emerging that control the activity of intracellular metal ions and help confine them to vital roles. These include integral transmembrane transporters, metalloregulatory sensors, and diffusible cytoplasmic metallochaperone proteins that protect and guide metal ions to targets. It is becoming clear that many of these proteins use atypical coordination chemistry to accomplish their unique goals. The different coordination numbers, types of coordinating residues, and solvent accessibilities of these sites are providing insight into the inorganic chemistry of the cytoplasm.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The metal ions relevant to biology span from highly available, with substantial pools of free ions (K+ and Mg2+), to those that have an average of less than one free ion per bacterial cell (Zn2+ and Cu+).
“The metal ions relevant to biology have properties that span the range from highly available, with substantial pools of free ions (K+ and Mg2+), to those that have an average of less than one free ion per bacterial cell (Zn2+ and Cu+).3,20”
From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [20]
Cites
Rosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., Donaldson, D., Goto, J., O'Regan, J. P., Deng, H.-X., et al. (1993) · Nature · doi:10.1038/362059a0 · Cited by 7,062 · see citing works
Femtomolar Sensitivity of Metalloregulatory Proteins Controlling Zinc Homeostasis
Outten, C. E., & O'Halloran, A. T. V. (2001) · Science · doi:10.1126/science.1060331 · Cited by 1,489 · see citing works
The <i>zntA</i> gene of <i>Escherichia coli</i> encodes a Zn(II)-translocating P-type ATPase
Rensing, C., Mitra, B., & Rosen, B. P. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.26.14326 · Cited by 419 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Small-Molecule Two-Photon Probes for Bioimaging Applications
Kim, H. M., & Cho, B. R. (2015) · Chemical Reviews · doi:10.1021/cr5004425 · Cited by 1,047 · see citing works
Krämer, U., Talke, I. N., & Hanikenne, M. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.04.010 · Cited by 583 · see citing works
Bioinorganic chemistry of copper and zinc ions coordinated to amyloid-β peptide
Faller, P., & Hureau, C. (2009) · Dalton Trans. · doi:10.1039/b813398k · Cited by 530 · see citing works
A Molecular Mechanism for Bacterial Susceptibility to Zinc
McDevitt, C. A., Ogunniyi, A. D., Valkov, E., Lawrence, M. C., Kobe, B., McEwan, A. G., & Paton, J. C. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002357 · Cited by 484 · see citing works
Fahrni, C. J. (2007) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2007.02.039 · Cited by 297 · see citing works
An Architectural Framework That May Lie at the Core of the Postsynaptic Density
Baron, M. K., Boeckers, T. M., Vaida, B., Faham, S., Gingery, M., Sawaya, M. R., Salyer, D., Gundelfinger, E. D., & Bowie, J. U. (2006) · Science · doi:10.1126/science.1118995 · Cited by 292 · see citing works
Staphylococcal response to oxidative stress
Gaupp, R., Ledala, N., & Somerville, G. A. (2012) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2012.00033 · Cited by 253 · see citing works
Sustainable life support on Mars – the potential roles of cyanobacteria
Verseux, C., Baqué, M., Lehto, K., de Vera, J.-P. P., Rothschild, L. J., & Billi, D. (2016) · International Journal of Astrobiology · doi:10.1017/s147355041500021x · Cited by 194 · see citing works
Metastatic cancers promote cachexia through ZIP14 upregulation in skeletal muscle
Wang, G., Biswas, A. K., Ma, W., Kandpal, M., Coker, C., Grandgenett, P. M., Hollingsworth, M. A., Jain, R., Tanji, K., Lόpez-Pintado, S., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0054-2 · Cited by 188 · see citing works
Haas, C. E., Rodionov, D. A., Kropat, J., Malasarn, D., Merchant, S. S., & de Crécy-Lagard, V. (2009) · BMC Genomics · doi:10.1186/1471-2164-10-470 · Cited by 159 · see citing works
The Effects of Mitochondrial Iron Homeostasis on Cofactor Specificity of Superoxide Dismutase 2
Yang, M., Cobine, P. A., Molik, S., Naranuntarat, A., Lill, R., Winge, D. R., & Culotta, V. C. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601064 · Cited by 143 · see citing works
An Antimicrobial Role for Zinc in Innate Immune Defense Against Group A Streptococcus
Ong, C.-L. Y., Gillen, C. M., Barnett, T. C., Walker, M. J., & McEwan, A. G. (2014) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiu053 · Cited by 124 · see citing works
Pathogenic adaptations to host-derived antibacterial copper
Chaturvedi, K. S., & Henderson, J. P. (2014) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2014.00003 · Cited by 134 · see citing works
Recent developments in copper and zinc homeostasis in bacterial pathogens
Braymer, J. J., & Giedroc, D. P. (2014) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2013.12.021 · Cited by 126 · see citing works
Linkage between Catecholate Siderophores and the Multicopper Oxidase CueO in <i>Escherichia coli</i>
Grass, G., Thakali, K., Klebba, P. E., Thieme, D., Müller, A., Wildner, G. F., & Rensing, C. (2004) · Journal of Bacteriology · doi:10.1128/jb.186.17.5826-5833.2004 · Cited by 124 · see citing works
Structural basis of PP2A activation by PTPA, an ATP-dependent activation chaperone
Guo, F., Stanevich, V., Wlodarchak, N., Sengupta, R., Jiang, L., Satyshur, K. A., & Xing, Y. (2014) · Cell Research · doi:10.1038/cr.2013.138 · Cited by 100 · see citing works
Fung, D. K. C., Lau, W. Y., Chan, W. T., & Yan, A. (2013) · Journal of Bacteriology · doi:10.1128/jb.00543-13 · Cited by 99 · see citing works
Turner, A. G., Ong, C.-L. Y., Gillen, C. M., Davies, M. R., West, N. P., McEwan, A. G., & Walker, M. J. (2015) · mBio · doi:10.1128/mbio.00278-15 · Cited by 93 · see citing works
Low-molecular-weight ligands in plants: role in metal homeostasis and hyperaccumulation
Seregin, I. V., & Kozhevnikova, A. D. (2021) · Photosynthesis Research · doi:10.1007/s11120-020-00768-1 · Cited by 73 · see citing works
Mechanism of metal ion activation of the diphtheria toxin repressor DtxR
D'Aquino, J. A., Tetenbaum-Novatt, J., White, A., Berkovitch, F., & Ringe, D. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500908102 · Cited by 57 · see citing works
Metals in Motion: Understanding Labile Metal Pools in Bacteria
Helmann, J. D. (2025) · Biochemistry · doi:10.1021/acs.biochem.4c00726 · Cited by 49 · see citing works
Ilari, A., Alaleona, F., Petrarca, P., Battistoni, A., & Chiancone, E. (2011) · Journal of Molecular Biology · doi:10.1016/j.jmb.2011.04.036 · Cited by 41 · see citing works
Pi, H., Wendel, B. M., & Helmann, J. D. (2020) · Journal of Bacteriology · doi:10.1128/jb.00711-19 · Cited by 35 · see citing works
Leach, L. H., Morris, J. C., & Lewis, T. A. (2007) · BioMetals · doi:10.1007/s10534-006-9035-x · Cited by 34 · see citing works
Metal immobilization: where and how
Mari, S., & Lebrun, M. (2005) · Topics in Current Genetics · doi:10.1007/4735_103 · Cited by 15 · see citing works
Zhou, T., Rodríguez-Barrios, S., Ruisánchez, I., & Rivera-Gil, P. (2025) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2025.117897 · Cited by 4 · see citing works
- Authors
- Finney, L. A., & O'Halloran, T. V.
- Affiliations
- Northwestern University (US)
- Department of Chemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208–3113, USA.
- Venue
- Science
- Published
- 2003-05-09
- Volume
- 300
- Issue
- 5621
- Pages
- 931-936
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2058170418
- Cited by
- 1,100
- References
- 3
- Citations by year
- 2026: 16 · 2025: 24 · 2024: 26 · 2023: 36 · 2022: 36 · 2021: 40 · 2020: 42 · 2019: 27 · 2018: 39 · 2017: 57 · 2016: 43 · 2015: 48 · 2014: 61 · 2013: 54 · 2012: 56
- FWCI
- 8.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM038784)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Health Sciences › Medicine › Oncology › Metal complexes synthesis and properties
- Keywords
- metal ion receptors, metallochaperone, metal transporters, metal cofactors, metal ion toxicity, solvent accessibility, coordination number
- MeSH terms
- Bacteria, Binding Sites, Carrier Proteins, Copper, Cytoplasm, Homeostasis, Iron, Kinetics, Metalloproteins, Metals, Mitochondria, Nickel, Saccharomyces cerevisiae, Thermodynamics, Zinc, Ion Transport, Transition Elements
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
