Reversible zinc exchange between metallothionein and the estrogen receptor zinc finger

We report here the first demonstration that reversible metal exchange occurs between metallothionein (MT) and full-length estrogen receptor (ER). Specific binding of ER to estrogen response element is inhibited in the presence of 40 mu M thionein and restored by 120 mu M zinc. Moreover, ER in metal-depleted nuclear extracts exhibits reduced DNA binding which can be restored by 140 mu M native MT, Hence, thionein inhibits DNA binding by abstracting zinc from functional ER while native MT is capable of restoring binding to metal-depleted extracts by donating metal to ER. This indicates MT may be an important physiological regulator of intracellular zinc and/or other metals.