Nuclear Receptors Flashcards
How many receptors make up the Nuclear Receptors
48
How many domains do nuclear receptors have
3
What is an orphan receptor
endogenous ligand has yet to be identified
what is an endogenous ligand
endogenous ligand in regard to NRs describes a naturally occurring small molecule that elicits a conformational change in the NR upon binding
What are the 2 class of function the nuclear receptor experience
Homodimer
Heterodimer
What is a homodimer
protein composed of two polypeptide chains that are identical in the order, number, and kind of their amino acid residues.
what is a heterodimer
a protein composed of two polypeptide chains differing in composition in the order, number, or kind of their amino acid residues
What is another term for nuclear receptor
Ligand - Activated gene regulatory proteins
transcription factors
Where can nuclear receptors be found
Cytosol or nucleus however they are not associated with the lipid membranes
What are the 6 families of nuclear receptor
Thyroid receptor like
retinoid X receptor like
Oestrogen Receptor Like
Nerve growth Factor IB Like
Steroidogenic factor like
Germ Cell Nuclear Factor Like
What is the structure of a nuclear receptor (general)
It has a C and N Termnal
The C terminal acts as a ligand binding domain
There is a DNA binding domain which is followed by the N terminal
The N terminal acts as the transcription activating domain
Describe the Activators of nuclear receptors
they are small hydrophobic molecule that must be transported around the body in the blood stream
What is the purpose of the binding of a carrier protein to the nuclear receptor
Specific carrier proteins bind to increase solubility
Dissociation then occurs before entering the cell
Describe the process by which binding proteins are delivered to the target tissue from the thyroid
The Thyroid secretes the activator (Hormone) which is delivered to its target via the blood stream. Where it then dissociates to its target.
Describe the mechanism of action by which a nuclear receptor is affected.
Agonists are typically hydrophobic and hence can freely diffuse across the plasma membrane.
Agonists then bind to the ligand binding domain acting as a molecular switch
A conformational change occurs upon binding within the receptor
The receptors then dimerize and translocate to the nucleus
What are glucocorticoid receptors involved in
Upregulation of anti-inflammatory proteins such as the lipcortins
what is the purpose of lipocortins
suppress the activity of phospholipase A2
What does phospholipase contribute too
It contributes to inflammation by producing the intermediate for arachidonic acid
What is dexamethasone used for
dexamethasone has anti inflammatory and immunosuppressant effects
It can be used to treat:
Rheumatic diseases
Skin Diseases
severe allergic reactions
What are oestrogen receptors regulators off
they are key regulators of cell growth and differentiation
what are the two oestrogen receptors that affect biological effects
ER ALPHA
ER BETA
What is tamoxifen
acts as oestrogen receptor antagonist in breast tissues
it also acts as oestrogen receptors in other tissues
it is commonly known as a selective oestrogen receptor molecule
What determines whether tamoxifen is an agonist or antagonist
the ratio of co activator to co repressor proteins in tissues
what must tamoxifen be metabolized by
Cytochromes to produce 4-hydroxytamoxifen, N-desmethyl-4hydroytamofien and endoxifen
