Question

Why do hormones/steroids have a ligand-binding domain and a DNA-binding domain? Does it need its receptor to attach to DNA?

Answer 1

ANSWER)

Lipophilic hormones—such as steroid or thyroid hormones—are able to pass through the cell and nuclear membrane; therefore receptors for these hormones do not need to be, although they sometimes are, located in the cell membrane.The majority of lipophilic hormone receptors are transcription factors that are either located in the cytosol and move to the cell nucleus upon activation, or remain in the nucleus waiting for the steroid hormone to enter and activate them. Upon binding by the hormone the receptor undergoes a conformational change, and the receptor together with the bound hormone influence transcription, either alone or in association with other transcription factors.

Steroid receptors enhance or repress gene transcription by forming homodimers that interact with specific DNA sequences in the promoter of target genes. All nuclear receptors, including steroid receptors, exhibit a modular structure composed of distinct domains. In general, these receptors contain a variable amino-terminal region, a highly conserved DNA-binding region, a highly variable hinge region, and a moderately conserved hormone or ligand-binding domain. Some receptors also contain a carboxy-terminal F domain. The primary structure of each human steroid receptor is shown, along with its physiological ligand. Specific residues within the DNA- and ligand-binding domains play an important part in receptor dimerization, which is critical because most nuclear receptors are only transcriptionally active as homo- or heterodimers. Finally, nuclear receptors have one or two regions called activation function 1 and 2 (AF1 and AF2) that are required to transactivate gene expression. Whereas the activity of AF1 is usually ligand-independent and located in the A/B domain, AF2 is found in the ligand-binding domain and is predominantly regulated by hormone binding