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The metallothionein structural motif in gene expression
D R Winge1, C T Dameron, G N George
1Department of Medicine, University of Utah Medical Center, Salt Lake City 84132.
Advances in Inorganic Biochemistry
|January 1, 1994
Summary
Metalloregulation in eukaryotes is clarified by copper-sulfur clusters in proteins like ACE1. This metal-binding motif, similar to metallothionein, explains metal-specific gene activation and protein structure dynamics.
Area of Science:
- Biochemistry
- Molecular Biology
- Bioinorganic Chemistry
Background:
- Metalloregulation in eukaryotes is not well understood, with few known metal-ion-regulated processes.
- Copper ions regulate gene expression in fungi (MT, SOD genes) and algae (cytochrome c6).
Purpose of the Study:
- To elucidate the mechanism of copper-1 (Cu1+) ion-mediated gene regulation in eukaryotes.
- To explore the role of metallothionein (MT) motifs and copper-sulfur (CuS) clusters in metal-specific protein activation.
Main Methods:
- Comparative analysis of protein structures, including ACE1, AMT1, and metallothioneins.
- Investigating the formation of copper-sulfur (CuS) polymetallic clusters in metalloregulatory proteins.
Main Results:
- The Cu1+-specific sensor protein ACE1 likely functions via a CuS polymetallic cluster.
- Structural similarities between ACE1, AMT1, and MT suggest the MT motif explains metal-specific activation.
- Metal:thiolate polymetallic clusters enable significant protein structural changes and metal-induced dynamics.
Conclusions:
- Coordination inorganic chemistry drives Cu1+ metalloregulation in biology.
- The MT motif and CuS clusters are key to understanding metalloregulation, with potential implications for diseases like Alzheimer's (MTIII).
- CuS polynuclear clusters may be a widespread mechanism in metalloregulation.