Low molecular weight cadmium—and copper-binding proteins from rat kidneys

Aj, Zelazowski; Ja, Szymańska

doi:10.1007/bf02798592

Cited by 12 publications

(3 citation statements)

References 14 publications

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“…Clearly, there is no evidence either for a stoichiometric partitioning among the metals or for the existence of metal-specific sites. In fact, the occupation of the binding sites by a given metal seems to be determined not so much by the chemical affinity of the sites as by the supply of the metal and by biological variables, such as the tissue of origin (13,14), age, stage of development (15), and the activity of certain still poorly understood homeostatic mechanisms (16 Isometallothioneins were identified by amino acid analysis in the following peaks: 1 (MT-2), 3 (MT-lA), 5 (MT-1B), 6 (MT-1C) and 8 (MT-iD). Peak 2,4 and 7 were not identified (51).…”

mentioning

confidence: 99%

Structure of Mammalian Metallothionein

Kägi¹,

Vašák²,

Lerch³

et al. 1984

Environmental Health Perspectives

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All mammalian metallothioneins characterized contain a single polypeptide chain of 61 amino acid residues, among them 20 cysteines providing the ligands for seven metalbinding sites. Native metallothioneins are usually heterogeneous in metal composition, with Zn, Cd, and Cu occurring in varying proportions. However, forms containing only a single metal species, i.e., Zn, Cd, Ni, Co, Hg, Pb, Bi, have now been prepared by in vitro reconstitution from the metal-free apoprotein. By spectroscopic analysis of such derivatives it was established that all cysteine residues participate in metal binding, that each metal ion is bound to four thiolate ligands, and that the symmetry of each complex is close to that of a tetrahedron.To satisfy the requirements of the overall Me7(Cys-)20 stoichiometry, the complexes must be combined to form metal-thiolate cluster structures. Experimental proof for the occurrence of such clusters comes from the demonstration of metal-metal interactions by spectroscopic and magnetic means. Thus, in Co(II)7-metallothionein, the Co(II)-specific ESR signals are effectively suppressed by antiferromagnetic coupling of juxtaposed paramagnetic metal ions. By monitoring changes in ESR signal size occurring on stepwise incorporation of Co(II) into the protein, it is possible to follow the building up of the clusters. This process is biphasic. Up to binding of four equivalents of Co(II), the ESR amplitude increases in proportion to the metal content, indicating generation of magnetically noninteracting high-spin complexes. However, upon addition of the remaining three equivalents of Co(II), these features are progressively suppressed, signaling the formation of clusters. The same mode of cluster formation has also been documented for Cd and Hg.The actual spatial organization of the clusters and the polypeptide chain remains to be established. An attractive possibility is the arrangement of the tetrahedral metal-thiolates in adamantane-like structures surrounded by properly folded segments of the chain providing the ligands. 1H-NMR data and infrared absorption measurements are consistent with a tightly folded structure rich in 3-type conformation.

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mentioning

confidence: 99%

Structure of Mammalian Metallothionein

Kägi¹,

Vašák²,

Lerch³

et al. 1984

Environmental Health Perspectives

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“…Studies of those proteins revealed that they differ in the content of endogenous metals depending on the organ in which the stimulation took place. In the metallothioneinlike protein of the kidneys, copper dominates as endogenous metal (23,(33)(34)(35)(36) while in the liver this role is played by zinc (25,(36)(37)(38)(39). In the rat, inorganic mercury stimulates the formation of metallothionein in the kidneys (26,(40)(41)(42)(43)(44)(45)(46)(47).…”

Section: Introductionmentioning

confidence: 99%

Interaction of Alkylmercuric Compounds with Sodium Selenite. III. Biotransformation, Levels of Metallothioneinlike Proteins and Endogenous Copper in Some Tissues of Rats Exposed to Methyl or Ethylmercuric Chloride with and without Sodium Selenite

Brzeznicka¹,

Chmielnicka²

1985

Environmental Health Perspectives

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The biotransformation efficiency of alkylmercurial compounds was studied in rat liver, kidneys, blood, and brain after 2-week administration of methylmercuric chloride (MeHg) and ethylmercuric chloride (EtHg) at doses of 0.25 or 2.5 mg Hg/kg, alone or in combination with sodium selenite (Se) at a level of 0.5 mg Se/kg. Simultaneously, the level of metallothioneinlike proteins (MTP) and endogenous copper (Cu) was monitored in tissues of control rats and intoxicated rats.Regardless of the dose, the highest concentrations of inorganic mercury from both the alkylmercurials was found in the rat kidneys. Sodium selenite had a variable effect on the amount of inorganic mercury liberated, depending on the organ and the molar ratio of Hg:Se administered.A statistically significant increase in the levels of MTP and endogenous Cu, compared with control group, was found only in the kidneys of intoxicated rats. This increase was dependent on the concentration of inorganic mercury liberated by biotransformation of alkylmercurials. The observed changes appeared when the level of inorganic mercury exceeded 10,Ig Hg/g tissue and reached a plateau at about 40 ,ug Hg/g tissue. In the presence of selenium the plateau of MTP and Cu levels were no oberved in the kidneys, regardless of the amount of inorganic mercury liberated.

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“…Clearly, there is no evidence either for a stoichiometric partitioning among the metals or for the existence of metal-specific sites. In fact, the occupation of the binding sites by a given metal seems to be determined not so much by the chemical affinity of the sites as by the supply of the metal and by biological variables, such as the tissue of origin (13,14), age, stage of development (15), and the activity of certain still poorly understood homeostatic mechanisms (16). While zinc is the more abundant component in nearly all mammals examined, copper tends to be more prevalent in fish.…”

mentioning

confidence: 99%

Structure of mammalian metallothionein.

Kägi¹,

Vašák²,

Lerch³

et al. 1984

Environ Health Perspect

View full text Add to dashboard Cite

All mammalian metallothioneins characterized contain a single polypeptide chain of 61 amino acid residues, among them 20 cysteines providing the ligands for seven metal-binding sites. Native metallothioneins are usually heterogeneous in metal composition, with Zn, Cd, and Cu occurring in varying proportions. However, forms containing only a single metal species, i.e., Zn, Cd, Ni, Co, Hg, Pb, Bi, have now been prepared by in vitro reconstitution from the metal-free apoprotein. By spectroscopic analysis of such derivatives it was established that all cysteine residues participate in metal binding, that each metal ion is bound to four thiolate ligands, and that the symmetry of each complex is close to that of a tetrahedron. To satisfy the requirements of the overall Me7(Cys-)20 stoichiometry, the complexes must be combined to form metal-thiolate cluster structures. Experimental proof for the occurrence of such clusters comes from the demonstration of metal-metal interactions by spectroscopic and magnetic means. Thus, in Co(II)7-metallothionein, the Co(II)-specific ESR signals are effectively suppressed by antiferromagnetic coupling of juxtaposed paramagnetic metal ions. By monitoring changes in ESR signal size occurring on stepwise incorporation of Co(II) into the protein, it is possible to follow the building up of the clusters. This process is biphasic. Up to binding of four equivalents of Co(II), the ESR amplitude increases in proportion to the metal content, indicating generation of magnetically noninteracting high-spin complexes. However, upon addition of the remaining three equivalents of Co(II), these features are progressively suppressed, signaling the formation of clusters. The same mode of cluster formation has also been documented for Cd and Hg. The actual spatial organization of the clusters and the polypeptide chain remains to be established. An attractive possibility is the arrangement of the tetrahedral metal-thiolates in adamantane-like structures surrounded by properly folded segments of the chain providing the ligands. 1H-NMR data and infrared absorption measurements are consistent with a tightly folded structure rich in beta-type conformation.

show abstract

Low molecular weight cadmium—and copper-binding proteins from rat kidneys

Cited by 12 publications

References 14 publications

Structure of Mammalian Metallothionein

Structure of Mammalian Metallothionein

Interaction of Alkylmercuric Compounds with Sodium Selenite. III. Biotransformation, Levels of Metallothioneinlike Proteins and Endogenous Copper in Some Tissues of Rats Exposed to Methyl or Ethylmercuric Chloride with and without Sodium Selenite

Structure of mammalian metallothionein.

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