Calmodulin decreases the estrogen binding capacity of the estrogen receptor.
We previously demonstrated the ability of calmodulin (CaM) to decrease the binding affinity of estradiol (E2) to the rat uterine estrogen receptor (ER). We show now that CaM induces a loss of E2 binding capacity especially when ER molecules exhibit a lower binding affinity for the hormone. By Western blotting and [125I]tamoxifen aziridine covalent labeling we found that this CaM-induced loss is not associated with a disappearance of the ER protein. In addition, we were able to demonstrate a CaM-mediated decrease in E2 binding of a human recombinant ER expressing solely its hormone binding domain (HBD, aa 282-595). Hence, CaM can modulate the structure of the HBD of the ER without any involvement of a degradative process, this conformational change is not mediated by other domains of the receptor and/or components of the native ER heterocomplex.
Bouhoute
A
A
Laboratoire J.C. Heuson de Cancérologie Mammaire, Institut Jules Bordet, Brussels, Belgium.
Leclercq
G
G
D000818:Animals; D001665:Binding Sites; D002147:Calmodulin / Q000502:physiology*; D004958:Estradiol / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D002147:Calmodulin; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D004958:Estradiol