Steroid hormone receptors ligand structures

Several studies have highlighted the importance of multidomain FKBPs in the control of signal transduction pathways. For example, hFKBP51 and hFKBP52 have been found in steroid hormone receptor complexes and are thought to play an important role in complex formation and translocation of receptor-ligand complexes from the cytosol into the nucleus [82,83], Notably, these multidomain FKBPs share structural characteristics as demonstrated by an N-terminal PPIase... 

Secretion of ecdysone starts the many biochemical processes that are necessary for the molting. The cells in the epidermis are stimulated to produce a new cuticle, and when ready, the insect will creep out of its old skin. The molecular mechanism of ecdysone has been studied in some detail. The molecular target of ecdysone and other ecdysteroids consists of at least two proteins, the ecdysteroid receptor (EcR) and ultraspiracle (USP). Both EcR and USP are members of the steroid hormone receptor superfamily with characteristic ligand-binding domains. An EcR-USP-ecdysteroid complex is formed, which activates several genes that code for transcription factors, i.e., proteins that activate or repress the activity of other genes, and the appropriate amounts of proteases and other enzymes necessary to degrade old structures and rebuild new ones are formed in a time-controlled sequence. 

These are DNA-binding proteins that show homologies with steroid hormone receptors and possess the double zinc finger motif, but for whom the true physiological ligands are unknown. One of these, COUP-TF, and a structurally very similar COUP-TF... 

It would be ideal if the receptor-binding capability could be directly incorporated into the peripheral structure of the ligand. Preliminary steps have been taken with the synthesis of complexes in which the exterior surfaces of the complex resemble a steroidal hormone (see Section 5.2.3.1.2), but much remains to be done to optimize receptor binding. 

These receptors are chiefly responsible for the physiological effects of steroid hormones such as cortisol as well as thyroid hormone and vitamin A. They are proteins that share a common basic structure consisting of a ligand binding domain and a DNA binding domain (comprised of zinc finger motifs). They operate as ligand-responsive transcription factors (see Chap. 17 for further discussion). 

---