Metal binding of metallothionein-3 versus metallothionein-2: lower affinity and higher plasticity.

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Palumaa P, Tammiste I, Kruusel K, Kangur L, Jornvall H, Sillard R

Metal binding of metallothionein-3 versus metallothionein-2: lower affinity and higher plasticity.

Biochim Biophys Acta. 2005 Mar 14;1747(2):205-11. Epub 2004 Dec 19.

PubMed ID

15698955 [ View in PubMed

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Abstract

Mammalian metallothioneins (MTs) are involved in cellular metabolism of zinc and copper and in cytoprotection against toxic metals and reactive oxygen species. MT-3 plays a specific role in the brain and is down-regulated in Alzheimer's disease. To evaluate differences in metal binding, we conducted direct metal competition experiments with MT-3 and MT-2 using electrospray ionization mass spectroscopy (ESI-MS). Results demonstrate that MT-3 binds Zn2+ and Cd2+ ions more weakly than MT-2 but exposes higher metal-binding capacity and plasticity. Titration with Cd2+ ions demonstrates that metal-binding affinities of individual clusters of MT-2 and MT-3 are decreasing in the following order: four-metal cluster of MT-2>three-metal cluster of MT-2 approximately four-metal cluster of MT-3>three-metal cluster of MT-3>extra metal-binding sites of MT-3. To evaluate the reasons for weaker metal-binding affinity of MT-3 and the enhanced resistance of MT-3 towards proteolysis under zinc-depleted cellular conditions, we studied the secondary structures of apo-MT-3 and apo-MT-2 by CD spectroscopy. Results showed that apo-MT-3 and apo-MT-2 have almost equal helical content (approximately 10%) in aqueous buffer, but that MT-3 had slightly higher tendency to form alpha-helical secondary structure in TFE-water mixtures. Secondary structure predictions also indicated some differences between MT-3 and MT-2, by predicting random coil for common MTs, but 22% alpha-helical structure for MT-3. Combined, all results highlight further differences between MT-3 and common MTs, which may be related with their functional specificities.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Zinc	Metallothionein-2	Protein	Humans	Unknown	Not Available	Details
Zinc acetate	Metallothionein-2	Protein	Humans	Unknown	Not Available	Details
Zinc chloride	Metallothionein-2	Protein	Humans	Unknown	Cofactor	Details
Zinc sulfate, unspecified form	Metallothionein-2	Protein	Humans	Unknown	Cofactor	Details