7.1 Flashcards
(30 cards)
What are nuclear receptors (NRs)?
Intracellular (cytoplasmic or nuclear) receptors that regulate gene transcription in response to ligand binding.
How were NRs first discovered?
They were the last category of receptors to be cloned (e.g., glucocorticoid and estrogen receptors).
Where are Type I and Type II NRs located?
Type I: Cytoplasm; Type II: Nucleus.
What types of signals do NRs transduce?
Initially endocrine, but now include non-endocrine ligands.
How many NRs are in the superfamily?
48 highly conserved receptors.
What are common properties of NR ligands?
Small, lipophilic (lipid-soluble) → easily cross membranes.
Name major categories of NR ligands.
Steroid hormones, thyroid hormones, fat-soluble vitamins, lipid metabolites, orphan receptor ligands.
Give examples of steroid hormone ligands.
Estrogen, testosterone, cortisol.
Give examples of thyroid hormones and vitamins.
T3, T4, vitamin D, retinoic acid.
What are orphan receptor ligands?
Ligands that were unknown at discovery but identified later.
How many domains do NRs typically have?
Four: N-terminal domain (A/B), DNA-binding domain (C), hinge region (D), ligand-binding domain (E).
What is the variability of the N-terminal domain?
Highly variable in sequence and length; drives receptor-, species-, and cell-specific effects.
What is AF-1?
Activation Function-1 – enables ligand-independent transcriptional activation.
What is unique about the DBD domain?
It’s the most highly conserved region among NRs.
What motifs does it contain?
Zinc finger motifs.
What is the function of the P-box?
First Zn finger – recognizes the response element (RE) with high affinity.
What is the function of the D-box?
Second Zn finger – mediates receptor dimerisation.
What is the function of the hinge region?
Provides flexibility, protein-protein interaction, and aids DNA recognition via the carboxy-terminal extension (CTE).
What is the general structure of the LBD?
11–13 α-helices forming a hydrophobic ligand-binding pocket.
What important function is associated with AF-2?
Ligand-dependent transcriptional activation.
What else is contained in the LBD?
Nuclear localization signals, dimerisation motifs, interaction sites for heat shock proteins, co-regulators, and transcription factors.
What is the general signalling mechanism of NRs?
Ligand binding → conformational change → dimerisation → DNA binding → cofactor recruitment → transcription regulation.
What are the two NR types based on localisation?
Type I: cytoplasmic, Type II: nuclear.
What is a major functional difference between NR types?
Type I binds DNA after ligand-induced nuclear translocation; Type II is already DNA-bound and represses or activates transcription based on ligand presence.
