Steroid Receptor Structure

Steroid receptors belong to the nuclear receptor super-family, one of the largest families of transcription factors, including receptors for estrogen, progesterone, thyroid hormone, vitamin D, retinoids, and orphan receptors, for which the ligands are not known.[5] Genes encoding members of the nuclear receptor superfamily consist of a single polypeptide chain that can be divided into several domains the amino-terminal domain (A/B), the DNA-binding domain (DBD, C), the hinge region (D), the ligand-binding domain (LBD, E), and the C-terminal domain (F) (Fig. 2).[2,5,6] The N-terminal domain is a highly variable region, containing at least one activation function (discussed subsequently), whereas the DBD is a conserved region (60 95%). The DBD contains two zinc fingers that form cysteine repeats, which are involved in the interactions between the receptor dimer and DNA at the steroid response element (SRE). For each receptor, this region is completely conserved among mammalian species and highly homologous to the DBD of other steroid receptors. The variable hinge region is located between the DBD and the LBD and is critical for interaction between the receptor and heat shock proteins (hsp), which modulate steroid receptor activation and inactivation. The hinge region also plays a role in nuclear translocation. The LBD is conserved among the related steroid receptors, including the progesterone receptor, estrogen receptor, glucocorticoid receptor, and mineralo-corticoid receptor. This region is responsible for ligand binding, which initiates conformational changes of the receptor that are necessary for proper signal transduction,

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Fig. 2 Schematic representation of the steroid hormone receptor genes. A single individual gene encodes each steroid receptor. The gene has several features that are common among members of the nuclear receptor superfamily: 1) a highly variable amino terminal domain (A/B); 2) the DNA binding domain (C); 3) the hinge domain (D); 4) the ligand binding domain (E), and the carboxyl terminal domain (F). The A/B and F domains contain activation functions (AF) that are responsible for regulating steroid hormone mediated transactivation. VD3R = vitamin D3 receptor; ER=estrogen receptor; MR=mi neralocorticoid receptor; AR = androgen receptor; PR=proges terone receptor; GR=glucocorticoid receptor. (From Ref. 5.)

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Fig. 2 Schematic representation of the steroid hormone receptor genes. A single individual gene encodes each steroid receptor. The gene has several features that are common among members of the nuclear receptor superfamily: 1) a highly variable amino terminal domain (A/B); 2) the DNA binding domain (C); 3) the hinge domain (D); 4) the ligand binding domain (E), and the carboxyl terminal domain (F). The A/B and F domains contain activation functions (AF) that are responsible for regulating steroid hormone mediated transactivation. VD3R = vitamin D3 receptor; ER=estrogen receptor; MR=mi neralocorticoid receptor; AR = androgen receptor; PR=proges terone receptor; GR=glucocorticoid receptor. (From Ref. 5.)

as well as interactions between the steroid receptor and the hsp. The C-terminal domain, like the N-terminal domain, is variable and contains one of the activation functions (discussed subsequently).[6]

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