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 μM thionein and restored by 120 μM zinc. Moreover, ER in metal-depleted nuclear extracts exhibits reduced DNA binding which can be restored by 140 μM 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.