Figure 1. Structure of the four natural estrogens, estrogen receptors (α and β) and ligand-binding domains. A: Structure of natural estrogens. E1 and E2: adult estrogens; E3 and E4: fetal estrogens. B: Estrogen receptors α and β (ERα and ERβ). Functional domains include the DNA-binding domain (DBD), ligand-binding domain (LBD), and two transcriptional activation functions, AF-1 and AF-2. The A/B domain, at the protein amino terminus (NH2), contains AF-1. The C domain binds to DNA motifs (consensus estrogen response elements [EREs]). The D domain (the hinge region) is involved in specific DNA binding and nuclear ER localization. The E domain is the LBD: it interacts with estrogens and selective estrogen receptor modulators (SERMs) and contains the AF-2 region. The carboxy terminus (COOH) is at the F domain. C&D: Ribbon diagrams. ERα-LBD structure complexed with estrogens (blue:E2; red:E3; green:E4). C: Ball-and-stick rendering of the ligand-binding site of the ligands and their interacting residues. Dotted lines: hydrogen bonds. D: LBDs depicted in C and the glucocorticoid receptor-interacting protein 1 (GRIP1) peptide fragment coactivator protein complexed with E3 or E4 only (darker red/green). Ligand: represented as space-filled model. Helix 12 position depicted by a narrow. Panel B adapted from Arnal JF, et al (2017) [3], and panels C and D from Abot A, et al (2014) [48].
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