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.
Lin
K H
KH
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Cheng
S Y
SY
D002413:Cations, Divalent; D002467:Cell Nucleus / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology*; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology*; D017967:Zinc Compounds
D002413:Cations, Divalent; D002712:Chlorides; D011518:Proto-Oncogene Proteins; D011988:Receptors, Thyroid Hormone; D017967:Zinc Compounds; D014284:Triiodothyronine; C016837:zinc chloride; D015032:Zinc