Metal transfer as a mechanism for metallothionein-mediated metal detoxification.
High kinetic reactivity and high metal affinity of the metal-binding sites of metallothionein are characteristics that would facilitate involvement of the thionein-zinc metallothionein couple in metal transfer or exchange reactions. Studies demonstrating thionein-metallothionein-mediated activation or inhibition of various zinc metalloenzymes and transcription factors provide support for a potential role for metallothionein in metal transfer reactions with receptor molecules. Although a role in basal zinc regulation is currently a topic of debate, less controversial is a role for metallothionein in the detoxification of metals such as cadmium. The toxicity of metals can, in part, be due to adventitious binding to charged sites of target proteins or the displacement of zinc bound to zinc metalloproteins. Zinc metallothionein has the capability of repairing such structures through abstraction of a toxic metal in the former case or through a reciprocal metal transfer reaction that involves abstraction of the toxic metal and donation of the essential metal zinc in the latter. This would confer on metallothionein an active role in the protective response to metal toxicity, rather than a passive one that is solely dependent on the high metal affinity for binding free metal ions. The efficacy of such a mechanism for metal detoxification has been demonstrated with enzymes, actin and zinc finger proteins. With zinc finger proteins, zinc metallothionein can restore both altered secondary structure and inhibited DNA-binding function to functional states through a zinc for cadmium exchange.
Roesijadi
G
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University of Maryland Center for Environmental Science, Chesapeake Biological Laboratory, Solomons 20688, USA. groes@cbl.cees.edu
D000818:Animals; D002460:Cell Line; D002942:Circular Dichroism; D006224:Cricetinae; D007700:Kinetics; D008668:Metallothionein / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D008670:Metals / Q000378:metabolism* / Q000633:toxicity; D008954:Models, Biological; D011485:Protein Binding; D015032:Zinc / Q000378:metabolism
D008670:Metals; D008668:Metallothionein; D015032:Zinc