Isolation of a prokaryotic metallothionein locus and analysis of transcriptional control by trace metal ions

Huckle, James W.; Morby, Andrew P.; Turner, Jennifer S.; Robinson, Nigel J.

doi:10.1111/j.1365-2958.1993.tb01109.x

Cited by 206 publications

(154 citation statements)

References 43 publications

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“…To date, Zn 4 clusters are unique to SmtA and to eukaryotic metallothioneins. However, while the two ZnCys 3 His sites and one of the ZnCys 4 sites in SmtA readily exchange Zn 2ϩ for exogenous Cd 2ϩ , the remaining ZnCys 4 site (A) is inert. The topology of this inert site and the surrounding ␤-sheet and ␣-helix closely resemble that of zinc finger portions of GATA and LIM proteins.…”

Section: Discussionmentioning

confidence: 99%

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A metallothionein containing a zinc finger within a four-metal cluster protects a bacterium from zinc toxicity

Blindauer

Harrison

Parkinson

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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172

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Zinc is essential for many cellular processes, including DNA synthesis, transcription, and translation, but excess can be toxic. A zinc-induced gene, smtA, is required for normal zinc-tolerance in the cyanobacterium Synechococcus PCC 7942. Here we report that the protein SmtA contains a cleft lined with Cys-sulfur and His-imidazole ligands that binds four zinc ions in a Zn4Cys9His2 cluster. The thiolate sulfurs of five Cys ligands provide bridges between the two ZnCys 4 and two ZnCys3His sites, giving two fused six-membered rings with distorted boat conformations. The inorganic core strongly resembles the Zn4Cys11 cluster of mammalian metallothionein, despite different amino acid sequences, a different linear order of the ligands, and presence of histidine ligands. Also, SmtA contains elements of secondary structure not found in metallothioneins. One of the two Cys4-coordinated zinc ions in SmtA readily exchanges with exogenous metal ( 111 Cd), whereas the other is inert. The thiolate sulfur ligands bound to zinc in this site are buried within the protein.Regions of ␤-strand and ␣-helix surround the inert site to form a zinc finger resembling the zinc fingers in GATA and LIM-domain proteins. Eukaryotic zinc fingers interact specifically with other proteins or DNA and an analogous interaction can therefore be anticipated for prokaryotic zinc fingers. SmtA now provides structural proof for the existence of zinc fingers in prokaryotes, and sequences related to the zinc finger motif can be identified in several bacterial genomes.

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Section: Discussionmentioning

confidence: 99%

“…1 and 2). Zinc is the most potent inducer of transcription from the smtA operator promoter, and repression of smtA in the absence of elevated zinc is mediated by the zinc-sensing, DNA-binding product of the divergently transcribed gene, smtB (3). Mutants lacking the smtA locus are hypersensitive to elevated zinc (5-fold), but otherwise viable (4).…”

mentioning

confidence: 99%

A metallothionein containing a zinc finger within a four-metal cluster protects a bacterium from zinc toxicity

Blindauer

Harrison

Parkinson

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

172

183

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“…Synechococcus sp. (cynobacterial strains) has been reported with the expression of the smtA gene and production of metal-binding protein [81]. Ralstonia eutropha has been genetically modified to express mouse metallothionein on the cell surface and decrease the toxic effect of the Cd (II) in the contaminated sites [82].…”

Section: Bioremediation By Physio-bio-chemical Mechanismmentioning

confidence: 99%

Bioremediation of Heavy Metals from Soil and Aquatic Environment: An Overview of Principles and Criteria of Fundamental Processes

et al. 2015

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Heavy metals are natural constituents of the environment, but indiscriminate use for human purposes has altered their geochemical cycles and biochemical balance. This results in excess release of heavy metals such as cadmium, copper, lead, nickel, zinc etc. into natural resources like the soil and aquatic environments. Prolonged exposure and higher accumulation of such heavy metals can have deleterious health effects on human life and aquatic biota. The role of microorganisms and plants in biotransformation of heavy metals into nontoxic forms is well-documented, and understanding the molecular mechanism of metal accumulation has numerous biotechnological implications for bioremediation of OPEN ACCESSSustainability 2015, 7 2190 metal-contaminated sites. In view of this, the present review investigates the abilities of microorganisms and plants in terms of tolerance and degradation of heavy metals. Also, advances in bioremediation technologies and strategies to explore these immense and valuable biological resources for bioremediation are discussed. An assessment of the current status of technology deployment and suggestions for future bioremediation research has also been included. Finally, there is a discussion of the genetic and molecular basis of metal tolerance in microbes, with special reference to the genomics of heavy metal accumulator plants and the identification of functional genes involved in tolerance and detoxification.

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“…As the concentration of metal ion increases, the effector-binding sites of the regulators become occupied eliciting a conformational change that weakens the affinity for the O͞P region, allowing transcription to proceed. Members of the SmtB͞ArsR family include: As(III), Sb(III), Bi(III)-responsive ArsR (7), Zn(II)-responsive SmtB (8), Cd(II), Pb(II), Bi(III)-responsive CadC (9)(10)(11), Zn(II)-responsive ZiaR (12), Co(II), Zn(II)-responsive CzrA (13,14), and, most recently, Ni(II), Co(II)-responsive NmtR (15).…”

mentioning

confidence: 99%

Structural elements of metal selectivity in metal sensor proteins

Pennella

Shokes

Cosper

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

107

270

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Staphylococcus aureusA bout one-third of all proteins exploit specific metal ions to assist in macromolecular folding and͞or function at the active site of metalloenzymes (1). All cells restrict the number of bioavailable metal atoms to avoid any excess that would otherwise compete with native metal ion sites that do not support biological activity (2). Essentially all cell types contain intracellular metal sensors that detect surplus metal ions and control the expression of genes encoding proteins that expel or sequester the extra ions (3). For some metals and some cell types, a complementary set of sensors detect deficiency and regulate genes encoding proteins that acquire more of the required ions (4, 5). It is currently poorly understood how such metal-sensing metalloregulators accurately discriminate between various metal ions.SmtB͞ArsR-family regulators are ubiquitous in bacterial genomes and bind to the operator͞promoter (O͞P) regions of gene(s) encoding proteins involved in metal export or sequestration, repressing transcription (for a review, see ref. 6). As the concentration of metal ion increases, the effector-binding sites of the regulators become occupied eliciting a conformational change that weakens the affinity for the O͞P region, allowing transcription to proceed. Members of the SmtB͞ArsR family include: As(III), Sb(III), Bi(III)-responsive ArsR (7), Zn(II)-responsive SmtB (8), Cd(II), Pb(II), Bi(III)-responsive CadC (9-11), Zn(II)-responsive ZiaR (12), Co(II), Zn(II)-responsive CzrA (13,14), and, most recently, Ni(II), Co(II)-responsive NmtR (15).Comparative structural and spectroscopic studies of six SmtB͞ ArsR family members reveal that individual members are characterized by one or both of two structurally distinct metal coordination sites (6, 11, 15-20). These two metal sites are designated ␣3N (or ␣3) and ␣5 (or ␣5C), named for the location of the metal-binding ligands within the known or predicted secondary structure of individual family members. The coordination environment and precise ligand set of the ␣3, ␣3N, and͞or ␣5, ␣5C sites in the different SmtB͞ArsR proteins differ and are presumed to contribute toward metal selectivity. A sequence comparison for proteins discussed herein is shown in Fig. 1 and highlights these sites.Here we report insights gained from the study of two additional family members, Staphylococcus aureus CzrA and Mycobacterium tuberculosis NmtR. CzrA and NmtR share 30% sequence identity and a high degree of similarity (60%) yet respond to distinct but partially overlapping metal profiles in vivo. S. aureus CzrA is a Co(II)͞Zn(II)-specific sensor that regulates the expression of the czr operon, which encodes a Co(II)͞ Zn(II)-facilitated pump, CzrB, that effluxes metal out of the cell (13, 14). Electromobility-shift assays and in vivo expression studies indicate that Zn(II) is the strongest inducer of CzrA regulation, with Co(II) also capable of regulation but only at higher concentrations than Zn(II). Other metals, including Ni(II), have little to no effect on derep...

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Isolation of a prokaryotic metallothionein locus and analysis of transcriptional control by trace metal ions

Cited by 206 publications

References 43 publications

A metallothionein containing a zinc finger within a four-metal cluster protects a bacterium from zinc toxicity

A metallothionein containing a zinc finger within a four-metal cluster protects a bacterium from zinc toxicity

Bioremediation of Heavy Metals from Soil and Aquatic Environment: An Overview of Principles and Criteria of Fundamental Processes

Structural elements of metal selectivity in metal sensor proteins

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