Zn+2 induces reversible cross-linking of human placental thyroid hormone nuclear receptor with no effect on hormone binding.

Zn+2 is required for specific binding of c-erbA proteins to the hormone response elements of target genes. It is unclear whether Zn+2 is important for the binding of ligand to c-erbA proteins. The present study evaluated the effect of Zn+2 and other divalent cations on the binding of 3,3',5-triiodo-L-thyronine(T3) to the purified human placental c-erbA protein (h-TR beta 1). Zn+2 induced cross-linking of h-TR beta 1 to form aggregates in a dose-dependent manner with an apparent half-maximal concentration of approximately 200 microM at 22 degrees C. Cross-linking was reversible by the addition of 5 microM EDTA or 10 mM dithiothreitol. The cross-linked h-TR beta 1 bound T3. These results indicated Zn+2 had no effect on T3 binding and suggested that the cysteines and histidines involved in cross-linking are not essential for T3 binding.