Question

What do you envision for the structure of estrogen receptor receptor-bound estradiol?

Answer 1

Estrogen receptors (ER's): Group of proteins found inside the cells. These receptors are activated by the hormone estrogen - 17β-estradiol. There are two types of ER's exists. They are: Estrogen receptor alpha (ERα) also called as NR3A1 and Estrogen receptor beta ( ERβ) also called as NR3A2 which are the members of nuclear receptor of intracellular receptor and membrane estrogen receptors which are mainly G protein-coupled receptors.The steroid hormone 17β-estradiol (E2) is a key regulator of growth, differentiation and function in a wide array of target tissues, including the male and female reproductive tracts, mammary gland, skeletal and cardiovascular systems. The ER helix 12 domain plays a cruical role in interactions with co-activators and co-repressors. Different ligands may differ in their affinity for alpha and beta isoforms of the estrogen receptors such as,

• estradiol binds equally on both the receptors.
• esyrone and raloxifene preferably binds to the alpha receptors.
• estriol and genistin binds to the beta receptors.

In vitro studies showed that certain functional domains of the ERα and ERβ exhibit a high degree of homology, namely the DNA- and ligand-binding domains, at 97% and 60% respectively, whereas considerable divergence is apparent in the amino-terminus (18% homology). Hence, ERα and ERβ interact with identical DNA response elements and exhibit a similar binding affinity profile for an array of endogenous, synthetic and naturally occurring estrogens. The molecular mechanisms of estrogen signaling, are focused on four pathways like: 1. classical ligand-dependent, 2. ligand-independent, 3. DNA-binding independent and 4. cell-surface (nongenomic) signaling.