Copper activates metallothionein gene transcription by altering the conformation of a specific DNA binding protein

doi:10.1016/0092-8674(88)90229-2

Cell

Volume 55, Issue 4, 18 November 1988, Pages 705-717

https://doi.org/10.1016/0092-8674(88)90229-2 Get rights and content

Abstract

Copper homeostasis in yeast involves a copper binding protein, metallothionein, and a trans-acting regulatory protein that activates transcription of the metallothionein gene in response to copper ions. We show that the regulatory protein specifically binds to the metallothionein gene control sequences in the presence, but not in the absence, of copper. Both the DNA binding and metalloregulatory functions of the trans-acting factor are contained within its aminoterminal domain, and partial proteolysis experiments show that copper activates this domain by causing a major switch in its conformation. Silver also activates the DNA binding domain in vitro and induces metallothionein gene transcription in vivo. We propose a novel copper cluster model for the DNA binding domain based on its surprising structural similarities to metallothionein itself.

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In some fungi, however, regulation of copper homeostasis is performed by a single copper-responsive regulator, CUF1. ACE1/CUP2 in S. cerevisiae is polypeptide with 225 amino acids residues (Furst et al., 1988) presenting three subdomains. The amino terminal half contains a (i) zinc module (residues 1–40), with a (R/K)GRP sequence (residues 36–39) (Farrell et al., 1996), and a (ii) copper regulatory binding domain (CuRD) (residues 41–100), that harbors a consensus sequence rich in cysteine residues (Cys-X2-Cys-X12-14-Cys-X-Cys-X10-27-Cys-X-Cys-X5-Cys-X-Cys), predicted to coordinate four Cu1+ atoms through sulfur bonds (Furst et al., 1988).
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Cell

ArticleCopper activates metallothionein gene transcription by altering the conformation of a specific DNA binding protein

Abstract

J. Mol. Biol.

J. Biol. Chem.

Cell

J. Biol. Chem.

Meth. Enzymol.

Cell

Cell

TIBS

Cell

Cell

Gene

Cell

J. Biol. Chem.

J. Mol. Biol.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Metal-dependent binding of a factor in vivo to the metal-responsive elements of the metallothionein I gene promoter

Mol. Cell. Biol.

Multiple global regulators control HIS4 transcription in yeast

Science

Molecular mechanism of regulation of siderophore-mediated iron assimilation

Microbiol. Rev.

Potential metal-binding domains in nucleic acid binding proteins

Science

Recombinant DNA research in yeast

Copper metallothionein of yeast, structure of the gene, and regulation of expression

Duplicated heavy metal control sequences of the mouse metallothionein-I gene

Tandem gene amplification mediates copper resistance in yeast

Equilibrium and kinetics of lac repressor-operator interactions by polyacrylamide gel electrophoresis

Nucl. Acids Res.

Crystal structure of Cd, Zn metallothionein

Science

A gel electrophoresis method for quantifying the binding of proteins to specific DNA regions: application to components of the E. coli lactose operon regulatory system

Nucl. Acids Res.

Article
Copper activates metallothionein gene transcription by altering the conformation of a specific DNA binding protein