004 Mechanisms of hormone action

Question 1

List the different domains found in a type I nuclear receptor?

Answer 1

N terminal regulatory region 
DNA binding domain 
Hinge region 
Ligand binding domain 
C terminal domain

Question 2

What is the main role of N terminal regulatory domain in type I nuclear receptor?

Answer 2

Contains AF-1 with activity independant to ligand prescence.

AF-1 can synergise with AF2 in the Ligand binding domain to produce robust upregulation of gene expression.

Question 3

What is the main role of the DBD in type I nuclear receptor?

Answer 3

Highly conserved
Contains 2 zinc fingers
binds to hormone response elements on DNA

Question 4

What is the main role of hinge region in type I nuclear receptor?

Answer 4

Flexible domain connecting DBD and LBD

Influences intracellular trafficking and subcellular distribution

Question 5

What is the main role of ligand binding domain in type I nuclear receptor?

Answer 5

contains antiparellel anti-helix alphas “alpha helical sandwich filling”
Contributes to dimerisation interface of receptor
Binds co-activator and corepressor proteins.
Contains AF-2 which activates when ligand approaches.

Question 6

What is the main role of C terminal domain in type I nuclear receptor?

Answer 6

Highly variable

Question 7

Describe the activity of Type II nuclear receptors?

Answer 7

Unlike Type I, are retained in the nucleus regardless of ligand binding status.
Binds as heterodimers (usually with rxr) TO dna
Often complexed with co-repressor proteins in absence of ligand.
Ligand binding will cause dissociation of corepressor and recruitment of coactivator.
This also recruits RNA polymerase.

Question 8

Describe the activity of type III nuclear receptors?

Answer 8

Orphan receptors: no known endogenous ligands
Weakly associated with FXR, LXR, PPAR
Cytochrome p450 enzymes can be upregulated
Can act as metabolic sensors