Metal binding sites of the estradiol receptor from calf uterus and their possible role in the regulation of receptor function
- Istituto di Patologia Generale ed Oncologia, Naples (Italy)
The existence of putative metal binding sites on the estradiol receptor (ER) molecule from calf uterus was evaluated by immobilizing various divalent metals to iminodiacetate-Sepharose. ER from both crude and highly purified preparations binds to metal-containing adsorbents complexed with Zn(II), Ni(II), Co(II), and Cu(II), but not to those complexed with Fe(II) and Cd(II). Analysis of affinity-labeled ER by ({sup 3}H)tamoxifen aziridine after elution from a column of Zn(II)-charged iminodiacetate-Sepharose showed that ER fragments obtained by extensive trypsinization were also bound. Zn(II) and the same other metals able to bind ER, when immobilized on resins, inhibit the binding of estradiol to the receptor at micromolar concentration. This inhibition is noncompetitive and can be reversed by EDTA. The inhibition of the hormone binding was still present after trypsin treatment of the cytosol, and it was abolished by preincubation with the hormone. Micromolar concentrations of these metals were able to block those chemical-physical changes occurring during the process of ER transformation in vitro. The presence of metal binding sites that modulate the ER activity in the hormone binding domain of ER is speculated. Since progesterone receptor showed the same pattern of binding and elution from metal-containing adsorbents, the presence of metal binding regulatory sites could be a property of all steroid receptors.
- OSTI ID:
- 5565042
- Journal Information:
- Biochemistry; (USA), Vol. 28:1; ISSN 0006-2960
- Country of Publication:
- United States
- Language:
- English
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ESTRADIOL
CROSS-LINKING
RECEPTORS
CADMIUM COMPOUNDS
CALVES
CATIONS
CHELATING AGENTS
COBALT COMPOUNDS
COPPER COMPOUNDS
INHIBITION
IRON COMPOUNDS
NICKEL COMPOUNDS
TRITIUM COMPOUNDS
UTERUS
ZINC COMPOUNDS
ANIMALS
BODY
CATTLE
CHARGED PARTICLES
CHEMICAL REACTIONS
DOMESTIC ANIMALS
ESTRANES
ESTROGENS
FEMALE GENITALS
HORMONES
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
IONS
MAMMALS
MEMBRANE PROTEINS
ORGANIC COMPOUNDS
ORGANS
POLYMERIZATION
PROTEINS
RUMINANTS
STEROID HORMONES
STEROIDS
TRANSITION ELEMENT COMPOUNDS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques