III. Signal transduction and cell cycle | 37. Nuclear receptors: steroid, thyroid, retinoid and Ah receptors Flashcards
I. Nuclear receptors
1. What are the features of Nuclear receptors?
- Nuclear receptors are a class of proteins responsible for sensing steroid/thyroid hormones as well as other molecules.
- They have the ability to directly bind to DNA and thereby regulate the expression of adjacent genes; controlling development, homeostasis or metabolism of the organism.
- Since they can bind directly to the DNA and regulate gene expression, these nuclear receptors are classified as TFs.
I. Nuclear receptors
2. What is the role of nuclear receptors?
They have the ability to directly bind to DNA and thereby regulate the expression of adjacent genes; controlling development, homeostasis or metabolism of the organism.
I. Nuclear receptors
3. Why are nuclear receptors referred as TFs?
Since they can bind directly to the DNA and regulate gene expression, these nuclear receptors are classified as TFs.
I. Nuclear receptors
4. What is the consequence of binding of a ligand?
Binding of a ligand usually causes a conformational change in the receptor and is therefore necessary for the activation of the receptors
I. Nuclear receptors
5. Where are nuclear receptors found?
Nuclear receptors either found in the cytosol or nucleus are both referred to as nuclear receptors, since it leads to regulation of transcription in the nucleus.
II. Ligands
1. What are the features of ligands?
- Since nuclear receptors are found inside the nucleus or cytoplasm, the ligands are small or hydrophobic enough to cross the plasma membrane.
- Once inside, the signal molecules bind to nuclear receptor either in the cytosol or nucleus.
- Therefore, these ligands include hydrophobic substances such as steroid hormones, thyroid hormones and so on.
II. Ligands
2A. What is the Structure of nuclear receptors?
Structure of nuclear receptors (5 DOMAINS)
1. N-terminal regulatory domain
2. DNA binding domain (DBD)
3. Hinge region
4. Ligand binding domain (LBD)
5. C-terminal domain:
II. Ligands
2B. Describe N-terminal regulatory domain in the Structure of nuclear receptors?
N-terminal regulatory domain contains the activation function 1 (AF-1), whose action is independent of the presence of the ligand
II. Ligands
2C. Describe DNA binding domain (DBD) in the Structure of nuclear receptors?
DNA binding domain (DBD) containing 2 zinc fingers that bind to specific sequences of DNA, called HRE (hormone-response-elements)
II. Ligands
2D. Describe Hinge region in the Structure of nuclear receptors?
Hinge region connects DBD + LBD, influences intracellular trafficking and subcellular distribution
II. Ligands
2E. Describe Ligand binding domain (LBD) in the Structure of nuclear receptors?
- LBD is an α-helical sandwich fold, where 3 antiparallel α-helices (the ‘’sandwich filling’’) are flanked by 2 α-helices on one side and 3 α-helices on the other side (the ‘’bread’’)
- LBD contributes to dimerization interface of the receptor + binds co-activator and co-repressor proteins
- Also contains the activation function 2 (AF-2), which is dependent of ligand binding
II. Ligands
2F. Describe C-terminal domain in the Structure of nuclear receptors?
Highly variable in sequence between different nuclear receptors
II. Ligands
3. How do we classify ligands?
Depending on where the nuclear receptors wait for the ligand, we can distinguish between two types:
- in the cytoplasm (type 1)
- in the nucleus (type 2)
II. Ligands
4A. What are the features of ligand type 1?
- Anchored in the cytoplasm
- Estrogen receptor-like
II. Ligands
4A. What are the features of ligand type 1?
Type 1 (Cytoplasm)
- Anchored in the cytoplasm
- Estrogen receptor-like