Key Points
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More than 25% of proteins are thought to need metals, such as zinc, iron, copper, cobalt, nickel, manganese, magnesium and calcium. Proteins tend to bind metals such as copper and zinc tightly, but bind metals such as manganese, magnesium and calcium weakly, and for essential divalent cations the order of affinity is defined by the Irving–Williams stability series. Some non-essential metals, such as cadmium and mercury, can also be highly competitive.
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The cell must supply sufficient atoms of each metal to satisfy the demands of proteins that require the element and must also act to keep the tight-binding metals out of the binding sites of proteins that require weaker-binding metals. Mechanisms by which cells meet this challenge to correctly populate metalloproteins have been proposed, although to date few studies have explicitly set out to test them.
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By restricting the numbers of metal atoms within the cytoplasm, it is presumed that rather than metals competing with other metals for a limited pool of protein, each protein competes with other proteins for a limited pool of metal. Under these conditions, metal occupancy is determined by the relative metal affinities of the different proteins rather than their absolute affinities. However, this requires precise control over the numbers of atoms of each metal and molecules of the respective metalloproteins.
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A balance between the actions of importers and exporters for each metal controls how many atoms accumulate in the cell. The catalogue of metal transporters includes ATP-binding cassette-type ATPases, P1-type ATPases, RND (resistance and nodulation), CDF (cation diffusion facilitator) and NiCoT (Ni and Co transporter) proteins, CorA (Co resistance), NRAMP (natural resistance associated with macrophage protein) and ZIP (Zrt/Irt-like protein)-family transporters.
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The number of protein binding sites for each metal can be adjusted to match metal supply; for example, by switching from a protein that requires iron to one that uses copper when it becomes available or iron becomes limiting. The synthesis of storage proteins, such as metallothioneins for zinc or ferritins for ferric iron, sequesters surplus metal atoms to restrain them from other binding sites.
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Expression of genes that encode metal transporters and storage proteins is generally controlled by metal sensors, including two-component histidine kinases and response regulators plus seven known families of soluble DNA-binding, metal-binding transcriptional regulators (Fur, DtxR, NikR, MerR, ArsR–SmtB, CsoR–RcnR and CopY). The metal affinities of these proteins can determine the boundaries between metal sufficiency and metal excess or deficiency for each element. These affinities become increasingly tight on moving up the Irving–Williams series, such that the metals at the top of the series must be bound and buffered to extremely low concentrations.
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Some metals are passed to the correct metalloproteins by dedicated delivery pathways that involve metallochaperones, in which case the specificity of a protein–protein interaction can ensure that only the correct proteins acquire the metal.
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Metal discrimination by the proteins of metal homeostasis is especially important if these proteins influence metal occupancy of other metalloproteins. Analysis of nickel specificity by the DNA-binding repressor NmtR from Mycobacterium tuberculosis revealed that the discernment of metals by metal sensors can be determined by the sensors' allosteric mechanism and/or its access to metal, which is predicted to be a function of the relative metal affinities of the cells complement of metal sensors.
Abstract
Protein metal-coordination sites are richly varied and exquisitely attuned to their inorganic partners, yet many metalloproteins still select the wrong metals when presented with mixtures of elements. Cells have evolved elaborate mechanisms to scavenge for sufficient metal atoms to meet their needs and to adjust their needs to match supply. Metal sensors, transporters and stores have often been discovered as metal-resistance determinants, but it is emerging that they perform a broader role in microbial physiology: they allow cells to overcome inadequate protein metal affinities to populate large numbers of metalloproteins with the right metals.
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References
Dupont, C. L., Yang, S., Palenik, B. & Bourne, P. E. Modern proteomes contain putative imprints of ancient shifts in trace metal geochemistry. Proc. Natl Acad. Sci. USA 103, 17822–17827 (2006).
Andreini, C., Bertini, I. & Rosata, A. A hint to search for metalloproteins in gene banks. Bioinformatics 20, 1373–1380 (2004).
Bertini, I. & Cavallaro, G. Metals in the omics world: copper homeostasis and cytochrome c oxidase assembly in a new light. J. Biol. Inorg. Chem. 13, 3–14 (2008).
Ferrer, M., Golyshina, O. V., Beloqui, A., Golyshin, P. N. & Timmis, K. N. The cellular machinery of Ferroplasma acidophilum is iron-protein dominated. Nature 445, 91–94 (2007). An experimental estimate of the scale of a cell's metallome.
Irving, H. & Williams, R. J. P. Order of stability of metal complexes. Nature 162, 746–747 (1948). The first version of the Irving–Williams series.
Fraústo da Silva, J. J. R. & Williams, R. J. P. The Biological Chemistry of the Elements (Oxford Univ. Press, 2001). An inspired overview of the chemical principals that govern the elemental requirements of life.
Guedon et al. The global transcriptional response of Bacillus subtilis to manganese involves the MntR, Fur, TnrA and σB regulons. Mol. Microbiol. 49, 1477–1491 (2003).
Lee, L. J., Barrett, J. A. & Poole, R. K. Genome wide transcriptional response of chemostat-cultured Escherichia coli to zinc. J. Bacteriol. 187, 1124–1134 (2005).
Magnani, D., Barré, O., Gerber, S. D. & Solioz, M. Characterisation of the CopR regulon of Lactococcus lactis IL1403. J. Bacteriol. 190, 536–545 (2008).
Robinson, N. J. A more discerning zinc exporter. Nature Chem. Biol. 3, 692–693 (2007).
Tottey, S. et al. Protein folding location can regulate manganese versus copper- or zinc-binding. Nature 455, 1138–1142 (2008). Predictions of the Irving–Williams series were tested, the significance of tight buffering of copper and zinc in the cytoplasm was revealed and a mechanism of metal selection based on Tat versus Sec export was discovered.
Nies, D. H. How cells control zinc homeostasis. Science 317, 1695–1696 (2007).
Nikaido, H. & Vaara, M. Molecular basis of bacterial outer membrane permeability. Microbiol. Rev. 49, 1–32 (1985).
Braun, V. & Endriss, F. Energy-coupled outer membrane transport proteins and regulatory proteins. Biometals 20, 219–230 (2007).
Ferguson, A. D. & Deisenhofer, J. Metal import through microbial membranes. Cell 116, 15–24 (2004).
Solioz, M., Odermatt, A. & Krapf, R. Copper pumping ATPases: common concepts in bacteria and man. FEBS Lett. 346, 44–47 (1994).
Saier, M. H. Jr, Tam, R., Reizer, A. & Reizer, J. Two novel families of bacterial membrane proteins concerned with nodulation, cell division and transport. Mol. Microbiol. 11, 841–847 (1994).
Anton, A., Groβe, C., Reiβman, J., Probyl, T. & Nies, D. H. CzcD is a heavy metal ion transporter involved in regulation of heavy metal resistance in Ralstonia sp. strain CH34. J. Bacteriol. 181, 6876–6881 (1999).
Saier, M. H. J. A functional–phylogenetic classification system for transmembrane solute transporters. Microbiol. Mol. Biol. Rev. 64, 354–411 (2000).
Rodionov, D. A., Hebbeln, P., Gelfand, M. S. & Eitinger, T. Comparative and functional genomic analysis of prokaryotic nickel and cobalt uptake transporters: evidence for a novel group of ATP-binding cassette transporters. J. Bacteriol. 188, 317–327 (2006).
Maguire, M. E. The structure of CorA: a Mg2+-selective channel. Curr. Opin. Struct. Biol. 16, 432–438 (2006).
Papp-Wallace, K. M. & Maguire, M. E. Manganese transport and the role of manganese in virulence. Annu. Rev. Microbiol. 60, 187–209 (2006).
Hantke, K. Bacterial zinc uptake and regulators. Curr. Opin. Microbiol. 8, 196–202 (2005).
Nucifora, G., Chu, L., Misra, T. K. & Silver, S. Cadmium resistance from Staphylococcus aureus plasmid pI258 cadA gene results from a cadmium-efflux ATPase. Proc. Natl Acad. Sci. USA 86, 3544–3548 (1989). The first description of a metal-transporting P 1 -type ATPase as a bacterial resistance determinant for a non-essential metal.
Banci, L. et al. Solution structure of the N-terminal domain of a potential copper-translocating P-type ATPase from Bacillus subtilis in the apo and Cu(I) loaded states. J. Mol. Biol. 317, 415–429 (2002).
Harrison, M. D., Jones, C. E., Solioz, M. & Dameron, C. T. Intracellular copper routing: the role of copper chaperones. Trends Biochem. Sci. 25, 29–32 (2000).
González-Guerro, M. & Argüello, J. M. Mechanisms of Cu+-transporting ATPases: soluble Cu+ chaperones directly transfer Cu+ to transmembrane transport sites. Proc. Natl Acad. Sci. USA 105, 5992–5997 (2008).
Lu, M. & Fu, D. Structure of the zinc transporter YiiP. Science 317, 1746–1748 (2007).
Nies, D. H. Efflux-mediated heavy metal resistance in prokaryotes. FEMS Microbiol. Rev. 27, 313–339 (2003). An extensive description of bacterial metal-transport proteins.
Giedroc, D. P. & Arunkumar, A. I. Metal sensor proteins: nature's metalloregulated allosteric switches. Dalton Trans. 29, 3107–3120 (2007). A review of metal-sensor proteins that emphasizes the importance of coordination chemistry.
Lee, J.-W. & Helmann, J. D. Functional specialization within the Fur family of metalloregulators. Biometals 20, 485–499 (2007).
Brown, N. L., Stoyanov, J. V., Kidd, S. P. & Hobman, J. L. The MerR family of transcriptional regulators. FEMS Microbiol. Rev. 27, 145–163 (2003).
Schmitt, M. P., Twiddy, E. M. & Holmes, R. K. Purification and characterization of the diphtheria toxin repressor. Proc. Natl Acad. Sci. USA 89, 7576–7580 (1992).
Iwig, J. S., Rowe, J. L. & Chiver, P. T. Nickel homeostasis in Escherichia coli — the rcnR–rcnA efflux pathway and its linkage to NikR function. Mol. Microbiol. 62, 252–262 (2006).
Liu, T. et al. CsoR is a novel Mycobacterium tuberculosis copper-sensing transcriptional regulator. Nature Chem. Biol. 3, 60–68 (2007). An exemplary study in which a new DNA-binding metal sensor was described, from discovery to the determination of its structure and the details of its metal-sensing sites.
Ogawa, T. et al. A two-component signal transduction pathway regulates manganese homeostasis in Synechocystis PCC 6803, a photosynthetic organism. J. Biol. Chem. 277, 28981–28986 (2002).
Anderson, L. A. et al. Characterisation of the molybdenum-responsive ModE regulatory protein and its binding to the promoter region of the modABCD (molybdenum transport) operon of Escherichia coli. Eur. J. Biochem. 246, 119–126 (1997).
McNicholas, P. M., Rech, S. A. & Gunsalus, R. P. Characterisation of the ModE DNA-binding sites in the control regions of modABCD and moaABCD of Escherichia coli. Mol. Microbiol. 23, 515–524 (1997).
Gaballa, A., Wang, T., Ye, R. W. & Helmann, J. D. Functional analysis of the Bacillus subtilis Zur regulon. J. Bacteriol. 184, 6508–6514 (2002).
Panina, E. M., Mironov, A. A. & Gelfand, M. S. Comparative genomics of bacterial zinc regulons: enhanced iron transport, pathogenesis, and rearrangement of ribosomal proteins. Proc. Natl Acad. Sci. USA 100, 9912–9917 (2003).
Maciag, A. et al. Global analysis of the Mycobacterium tuberculosis Zur (FurB) regulon. J. Bacteriol. 189, 730–740 (2007).
Campbell, D.R. et al. Mycobacterial cells have dual nickel–cobalt sensors: sequence relationships and metal sites of metal-responsive repressors are not congruent. J. Biol. Chem. 282, 32298–32310 (2007).
Delany, I., Rappuoli, R. & Scarlato, V. Fur functions as an activator and as a repressor of putative virulence genes in Neisseria meningitides. Mol. Microbiol. 52, 1018–1090 (2004).
Masse, E. & Gottesman, S. A small RNA regulates the expression of genes involved in iron metabolism in Escherichia coli. Proc. Natl Acad. Sci. USA 99, 4620–4625 (2002).
Dann, C. E. et al. Structure and mechanism of a metal-sensing regulatory RNA. Cell 130, 878–892 (2007).
Helmann, J. D. Measuring metals with RNA. Mol. Cell 27, 859–860 (2007).
Golynskiy, M. V., Gunderson, W. A., Hendrich, M. P. & Cohen, S. M. Metal-binding studies and EPR spectroscopy of the manganese transport regulator MntR. Biochemistry 45, 15359–15372 (2006).
Outten, C. E. & O'Halloran, T. V. Femtomolar sensitivity of metalloregulatory proteins controlling zinc homeostasis. Science 292, 2488–2492 (2001). The sensors Zur and ZntR respond to zinc at concentrations that are so low that they imply that all cellular zinc is tightly bound and buffered.
Changella, A. et al. Molecular basis of metal-ion selectivity and zeptomolar sensitivity by CueR. Science 301, 1383–1397 (2003). CueR responds to copper at concentrations that are so low that they imply that all cellular copper is tightly bound and buffered.
Andrews, S. C., Robinson, A. K. & Rodríguez- Quiñones, F. Bacterial iron homeostasis. FEMS Microbiol. Rev. 27, 215–237 (2003).
Huckle, J. W., Morby, A. P., Turner, J. S. & Robinson, N. J. Isolation of a prokaryotic metallothionein locus and analysis of transcriptional control by trace metals. Mol. Microbiol. 7, 177–187 (1993).
Blindauer, C. A. et al. Multiple bacteria encode metallothioneins and SmtA-like zinc fingers. Mol. Microbiol. 45, 1421–1432 (2002).
Morby, A. P., Turner, J. S., Huckle, J. W. & Robinson, N. J. SmtB is a metal-dependent repressor of the cyanobacterial metallothionein gene smtA: identification of a Zn inhibited DNA–protein complex. Nucleic Acids Res. 21, 921–925 (1993).
Gold, B. et al. Identification of a copper-binding metallothionein in pathogenic mycobacteria. Nature Chem. Biol. 4, 609–616 (2008).
McHugh, J. P. et al. Global iron-dependent gene regulation in Escherichia coli. A new mechanism for iron homeostasis. J. Biol. Chem. 278, 29478–29486 (2003). Transcription profiling uncovers a low-iron metabolism that is switched on when iron is limited.
Nielsen, A. K., Gerdes, K. & Murrell, J. C. Copper-dependent reciprocal regulation of methane monoxygenase genes in Methylococcus capsulatus and Methylosinus trichosporium. Mol. Microbiol. 25, 399–409 (1997).
Lieberman, R. L. & Rosenzweig, A. C. Crystal structure of a membrane-bound metalloenzyme that catalyses the biological oxidation of methane. Nature 434, 177–182 (2005).
Merchant, S. in Metal Ions in Gene Regulation (eds Silver, S. & Walden, W.) 450–467 (Chapman & Hall, New York, 1998).
Rowe, J. L., Starnes, L. & Chivers, P. T. Complex transcriptional control links NikABCDE-dependent nickel transport with hydrogenase expression in Escherichia coli. J. Bacteriol. 187, 6317–6323 (2005). The nickel supply for hydrogenase was shown to be independent of the nickel supply for the nickel sensor.
Woodward, J., Orr, M., Cordray, K. & Greenbaum, E. Enzymatic production of biohydrogen. Nature 405, 1014–1015 (2000).
Leech, M. R. & Zamble, D. B. Metallocentre assembly of the hydrogenase enzymes. Curr. Opin. Chem. Biol. 11, 159–165 (2007).
Leech, M. R., Zhang, J. W. & Zamble, D. B. The role of complex formation between the Escherichia coli hydrogenase accessory factors HypB and SlyD. J. Biol. Chem. 282, 16177–16186 (2007).
Maier, R. J., Benoit, S. L. & Seshadri, S. Nickel-binding and accessory proteins facilitating Ni-enzyme maturation in Helicobacter pylori. Biometals 20, 655–664 (2007).
Lee, M. H. et al. Purification and characterization of Klebsiella aerogenes UreE protein: a nickel-binding protein that functions in urease metallocentrer assembly. Protein Sci. 2, 1042–1052 (1993).
Cuirli, S. et al. Molecular characterization of Bacillus pasteurrii UreE, a metal-binding chaperone for the assembly of the urease active site. J. Biol. Inorg. Chem. 7, 623–631 (2002).
Fontecave, M. Iron–sulfur clusters: ever-expanding roles. Nature Chem. Biol. 2, 171–174 (2006).
Fontecave, M. & Ollagnier- de-Choudens, S. Iron–sulphur cluster biosynthesis in bacteria: mechanisms of cluster assembly and transfer. Arch. Biochem. Biophys. 472, 226–237 (2008).
Ranquet, C., Ollangnier- de-Choudens, S., Loiseau, L., Barras, F. & Fontecave, M. Cobalt stress in Escherichia coli. The effect on the iron–sulfur proteins. J. Biol. Chem. 282, 30442–30451 (2007). Iron–sulphur cluster assembly was shown to be susceptible to iron replacement by cobalt but the clusters were protected once inside the holoprotein.
Odermatt, A. & Solioz, M. Two trans-acting metalloregulatory proteins controlling expression of the copper-ATPases of Enterococcus hirae. J. Biol. Chem. 270, 4349–4354 (1995). Reported the discovery of a bacterial copper metallochaperone.
Cobine, P. et al. The Enterococcus hirae copper chaperone CopZ delivers copper(I) to the CopY repressor. FEBS Lett. 445, 27–30 (1999).
Brorsson, A. C. et al. The “two state folder” MerP forms partially unfolded structures that show temperature dependent hydrogen exchange. J. Mol. Biol. 340, 333–344 (2004).
Radford, D. S. et al. CopZ from Bacillus subtilis interacts in vivo with a copper exporting CPx-type ATPase CopA. FEMS Microbiol. Lett. 220, 105–112 (2003).
Tottey, S. et al. A copper metallochaperone for photosynthesis and respiration reveals metal-specific targets, interaction with an importer, and alternative sites for copper acquisition. J. Biol. Chem. 177, 5490–5497 (2002).
Banci, L., Bertini, I., Ciofi-Baffoni, S., Del Conte, R. & Gonnelli, L. Understanding copper trafficking in bacteria: interactions between the copper transport protein CopZ and the N-terminal domain of the copper ATPase CopA from Bacillus subtilis. Biochemistry 42, 1939–1949 (2003). High-field NMR was used to visualize the transient complexes that form between copper metallochaperones and their partners.
Banci, L. et al. The delivery of copper for thylakoid import observed by NMR. Proc. Natl Acad. Sci. USA 103, 8320–8325 (2006).
Claus, H. & Decker, H. Bacterial tyrosinases. Syst. Appl. Microbiol. 29, 3–14 (2006).
Cavet, J. S. et al. A nickel–cobalt sensing ArsR–SmtB family repressor. Contributions of cytosol and effector binding sites to metal selectivity. J. Biol. Chem. 277, 38441–38448 (2002). Identified the importance of access and allostery to the metal specificity of metal sensors.
Turner, J. S., Glands, P. D., Samson, A. C. & Robinson, N. J. Zn2+-sensing by the cyanobacterial metallothionein repressor SmtB: different motifs mediate metal-induced protein–DNA dissociation. Nucleic Acids Res. 24, 3714–3721 (1996).
Pennella, M. A., Shokes, J. E., Cosper, N. J., Scott, R. A. & Giedroc, D. P. Structural elements of metal selectivity in metal sensor proteins. Proc. Natl Acad. Sci. USA 100, 3713–3718 (2003).
Golynskiy, M. V., Gunderson, W. A., Hendrich, M. P. & Cohen, S. M. Metal binding studies and EPR spectroscopy of the manganese transport regulator MntR. Biochemistry 45, 15359–15372 (2006). Confirmed the importance of access and allostery to the metal selectivity of MntR.
Mills, S. A. & Marletta, M. A. Metal binding characteristics and role of iron oxidation in the ferric uptake repressor from Escherichia coli. Biochemistry 44, 13553–13559 (2005).
Phillips, C. M. et al. Structural basis of the metal specificity for nickel regulatory protein NikR. Biochemistry 47, 1938–1946 (2008). Confirmed the importance of access and allostery to the metal selectivity of NikR.
Liu, T., Reyes-Caballero, H., Li, C., Scott, R. A. & Giedroc, D. P. Multiple metal binding domains enhance the Zn(II) selectivity of the divalent metal, ion transporter AztA. Biochemistry 46, 11057–11068 (2007).
Dutta, S. J., Liu, J., Stemmler, A. J. & Mitra, B. Conservative and nonconservative mutations of the transmembrane CPC motif in ZntA: effect on metal selectivity and activity. Biochemistry 46, 3692–3703 (2007).
Borrelly, G. P., Rondet, A. A., Tottey, S. & Robinson, N. J. Chimeras of P-type ATPases and their transcriptional regulators: contributions of a cytosolic amino-terminal domain to metal specificity. Mol. Microbiol. 53, 217–227 (2004).
Guedon, E. & Helmann, J. D. Origins of metal ion selectivity in the DtxR/MntR family of metalloregulators. Mol. Microbiol. 48, 495–506 (2003). DtxR responded aberrantly to manganese when tested in a heterologous bacterium as it could gain access to the metal.
Corbin, B. D. et al. Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319, 962–965 (2008).
Tottey, S., Harvie, D. R. & Robinson, N. J. Understanding how cells allocate metals using metal sensors and metallochaperones. Acc. Chem. Res. 38, 775–783 (2005).
O'Halloran, T. V. & Finney, L. A. Transition metal speciation in the cell: insights from the chemistry of metal ion receptors. Science 300, 931–936 (2003).
Kuper, J., Llamas, A., Hecht, H. J., Mendel, R. R. & Schwarz, G. Structure of the molybdopterin-bound Cna1G domain links molybdenum and copper metabolism. Nature 430, 803–806 (2004).
Ansari, A. Z., Chael, M. L. & O'Halloran, T. V. Allosteric underwinding of DNA is a critical step in positive control of transcription by Hg-MerR. Nature 355, 87–89 (1993).
Xu, Y., Feng, L., Jeffrey, P. D., Shi, Y. & Morel, F. M. Structure and metal exchange in the cadmium carbonic anhydrase of marine diatoms. Nature 452, 56–61 (2008).
Gupta, A., Matsui, K., Lo, J. F. & Silver, S. Molecular basis for resistance to silver cations in Salmonella. Nature Med. 5, 183–188 (1999).
Qin, J. et al. Convergent evolution of a new arsenic binding site in the ArsR/SmtB family of metalloregulators. J. Biol. Chem. 282, 34346–34355 (2007).
Magyar, J. S. & Godwin, H. A. Spectropotentiometric analysis of metal binding to structural zinc-binding sites: accounting quantitatively for pH and metal ion buffering effects. Anal. Biochem. 320, 39–54 (2003).
Wernimont, A. K., Yatsunyk, L. A. & Rosenzweig, A. C. Binding of copper(I) by the Wilson disease protein and its copper chaperone. J. Biol. Chem. 279, 12269–12276 (2004).
Xiao, Z., Loughlin, F., George, G. N., Howlettt, G. J. & Wedd, A. G. C-terminal domain of the membrane copper transporter Ctr1 from Saccharomyces cerevisiae binds four Cu(I) atoms as a cuprous-thiolate polynuclear cluster: sub-femtomolar Cu(I) affinity of three proteins involved in copper trafficking. J. Am. Chem. Soc. 126, 3081–3090 (2004).
Burns, C. S. et al. Copper coordination in the full-length, recombinant prion protein. Biochemistry, 42, 6794–6803 (2003).
Klewpatinoud, M., Davis, P., Bowen, S., Brown, D. R. & Viles, J. H. Deconvoluting the Cu2+ binding modes of full-length prion protein. J. Biol. Chem. 283, 1870–1881 (2008).
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The authors have been supported by Biotechnology and Biological Sciences Research Council (BBSRC) Plant and Microbial Sciences (PMS) grant BB/E001688/1.
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Glossary
- Lewis acid
-
A chemical that can accept a pair of electrons from a Lewis base.
- Thiophilic
-
A strong binder to thiol sulphurs.
- Porin
-
A β-barrel protein that allows the diffusion of molecules (up to ∼1.5 kDa) across the outer membrane.
- Antiport
-
Coupled transport of two molecules in opposing directions.
- Metallothionein
-
A small, cysteine-rich metal-binding protein.
- Apoprotein
-
A protein without a metal cofactor.
- Holoprotein
-
A mature protein with a metal cofactor.
- Winged helix–turn–helix structure
-
A structure found in many DNA-binding proteins with wings formed by a pair of β-strands.
- d–d transition
-
An electronic transition between d-orbitals in a metal atom.
- Tetrahedral geometry
-
Four atoms are arranged around a central atom, thereby defining the vertices of a tetrahedron.
- Octahedral geometry
-
Six atoms are symmetrically arranged around a central atom, thereby defining the vertices of an octahedron.
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Waldron, K., Robinson, N. How do bacterial cells ensure that metalloproteins get the correct metal?. Nat Rev Microbiol 7, 25–35 (2009). https://doi.org/10.1038/nrmicro2057
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DOI: https://doi.org/10.1038/nrmicro2057
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