Metallothionein interaction with metals

Metallothionein expression is mainly regulated at the transcriptional level and is induced by various heavy metals, such as zinc. There are seven short sequence motifs located in a region within 200 base pairs upstream of the transcription start site. These cis-acting DNA elements are responsible for heavy metal induction and are thus termed metal responsive elements (MREs) (Stuart et al., 1984). Several regulatory proteins have been cloned which interact with these MREs. One of these, MRE-binding transcription factor-1 (MTF-1), is essential for the transcriptional activation of metallothionein genes by heavy metals like zinc and cadmium (Radtke et al., 1993 Palmiter, 1994 Heuchel et al., 1994 Koiszumi et al., 1999). 

Palmiter, R.D. (1994) Regulation of metallothionein genes by heavy metals appears to be mediated by a zinc-sensitive inhibitor that interacts with a constitutively active transcription factor, MTF-1. Proc. Nat. Acad. Sci. USA, 91, 1219-1223. 

Interaction with metallothionein is the basis for metabolic interactions between these metals. Metallothionein III is found in the human brain and differs from I and II by having six glutamic acid residues near the terminal part of the protein. Metallothionein III is thought to be a growth inhibitory factor, and its expression is not controlled by metals however, it does bind zinc. Another proposed role for metallothionein III is participation in the utilization of zinc as a neuromodulator, since metallothionein III is present in the neurons that store zinc in their terminal vesicles. Metallothionein IV occurs during differentiation of stratified squamous epithelium, but it is known to have a role in the absorption or toxicity of cadmium. 

Metallothionein 105, 106 , interactions with various metals 105ff. 

Koizumi S, Yamada H, Suzuki K, Otsuka F (1992b) Zinc-specific activation of a HeLa cell nuclear protein which interacts with a metal responsive element of the human metallothionein-IIA gene. Eur J Biochem 210 555-560 Kornberg RD, Lorch Y (1992) Chromatin structure and transcription. Annu Rev Cell Biol 8 563-587... 

IV. Disposition of the metals in cells interactions with membranes glutathione, metallothionein and DNA. Biol Trace Elem Res 6 139-158... 

It is interesting that a unique secondary structural element, designated the half-turn, was indentified in preliminary NMR studies of rabbit metallothionein-2 (Wagner etal., 1986). The half-turn element is defined as a type II turn with (f>3 rotated from 90° to -90° its occurrence in the metallothionein-2 structure arises from the constraints placed on the relatively short polypeptide chain by the metal clusters. Although these constraints are not well understood and are certainly difficult to predict, the continued biophysical study of metallothionein-2 will certainly improve our understanding of protein-metal cluster interactions. 

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