Fig. 1: Structure and function of NR3 receptors.
a Phylogenetic tree of the NR family comprising 48 members in human. NR3 receptors are labeled in red. b The archetypal domain structure of NRs is composed of an unordered N-terminal domain (NTD; dark blue), containing the ligand-independent activation function 1 (AF-1), a DNA binding domain (DBD; orange) with two zinc finger motifs for binding to hormone response elements (HREs) on the DNA, a flexible hinge region (grey), and a ligand binding domain (LBD; light blue) with the ligand-dependent activation function 2 (AF-2). c General activation mechanism of NR3 receptors. Colors corresponding to modular domain structure in (b). Before agonist binding (yellow), most NR3 receptors are located in the cytosol bound to heat shock proteins (HSPs; purple) preventing diffusion of the receptor into the nucleus. Agonist binding leads to conformational changes, release of the HSP, and receptor homodimerization. The resulting dimer diffuses to the nucleus, binds the corresponding HRE (red) on the DNA (dark grey), and recruits coactivators (cyan) to initiate gene transcription. Estrogen receptors (ER; NR3A) and progesterone receptor (PR; NR3C3) can also be DNA-bound in the nucleus independently of ligand binding and thus deviate from the general mechanism72,73,74,75. Created in BioRender. Merk, D. (2025) https://BioRender.com/a87p902.
