Nuclear receptor

Nuclear Receptor

Nuclear receptors are intracellular receptors that bind to small lipophilic ligands which diffuse through the membrane to interact with the target. The receptor-ligand complex activates the transcription factors in the nucleus and either activate or repress the transcription of mRNA and the synthesis of proteins. These receptors have prolonged actions lasting through hours to days.

Structure of the Receptor:

Nuclear hormone receptors contain four major domains: The N-terminal ligand-binding domain (12 helices) contains an activation region (AF-1) essential for transcriptional regulation followed by two zinc fingers that bind to DNA (the DNA-binding domain). The C-terminal contains a hinge region and a ligand-binding domain with specific sets of amino acid residues for binding co-activators and co-repressors in second activation region (AF- 2). 

Structure of the nuclear receptor

Types of Nuclear receptor:

Signal Transduction Pathway:

• In the inactive state, receptors are present in the cytoplasm or on the nuclear membrane.
• Binding of the ligand activates (N-terminal activation region (AF-1) by phosphorylation) the receptor by dissociation from binding proteins (HSP) and it induces a major conformational change.
• The activated ligand-receptor complex then translocates to the nucleus, when it binds to DNA, the nuclear hormone receptors act as dimers—homodimers, or as heterodimers.
• The receptor dimers bind to repetitive DNA sequences, hormone response elements (HRE) that are found upstream or within the regulated genes, and combines with co-activators or co-repressors.
• Co-activators recruit enzymes to the transcription complex that modify chromatin, such as histone acetylase, which serves to unravel DNA for transcription. Co-repressors recruit proteins such as histone deacetylase, which keeps DNA tightly packed and inhibits transcription.
• The activation or inactivation of these factors causes the transcription of DNA into RNA and translation of RNA into an array of proteins.

Signal transduction pathway of nuclear receptor

Physiological Significance:

The receptor proteins are able to regulate numerous physiological processes such as reproduction, development, and metabolism, steroid hormones such as androgens, estrogens, glucocorticoids, thyroid hormone, and vitamin D are some of the common ligands for the nuclear receptors.

The nuclear receptors are the lesser understood receptors; it has major roles in the regulation and coordination of hormonal actions. Here we have tried to simplify the topic referring to the books of pharmacology. For more such simplified topics of pharmacy do subscribe to @A-Z Pharma Science