G Coupled Protein Receptors Flashcards
Tell us five things you know about GCPRs
*transmembrane proteins
*single polypeptide chain
*Wound around the membrane 7 times
*Have 2 domains:
-N terminal extracellular domain - interacts with agonist
-C terminal intracellular domain -interacts with G protein
What reactions are triggers when ligands bind to the N terminal extracellular domain
Intracellular cascade of reactions
Tell us 3 features of G proteins
• Membrane resident proteins
• Have 3 subunits: alpha, beta, gamma
• In the resting state, they are called alpha-beta gamma dimer
What is joined to the alpha subunit in the resting state?
GDP
What happens when an agonist binds to the N terminal extracellular domain?
Keywords/hints:
GDP, intracellular domain, enzymes, GTP, alpha, beta, gamma subunits, activation, conformational change, ion gated channels, kinase, dimer
• A conformational change occurs
• The c terminal intracellular domain interacts with a G protein
• GDP will dissociate from the alpha subunit, GTP will bind = activation of the protein
• The a subunit will seperate from the beta-gamma dimer.
• The a subunit will interact with either phospholipase C or adenylate cyclase
• The beta-gamma dimer will bind to ion gated channels and kinases to activate them
What two enzymes does the alpha subunit with GTP bound to it activate?
Phospholipase C and Adenylate Cyclase
3 features of adenylate cylase
• Membrane-bound enzyme
• Stimulated by Gs protein
• Inhibited by Gi protein
What happens when adenylate cyclase is activated?
•ATP is converted into cAMP
•cAMP activates dependent protein kinases, which phosphorylate enzymes
1 feature of Phospholipase C
It is activated by the Gq protein
What does Phospholipase C do?
Catalyses the cleavage of phosphatidylinositol bisphosphate into DAG and IP3
2 features of the IP3 receptor
- Ligand-gated
calcium channel - Found in the membrane of the endoplasmic reticulum
What happens when IP3 binds to the IP3 receptor?
There is a release of calcium ions into the cytoplasm
Main goal of the IP3 receptors?
Increase the cytosolic calcium concentration
Why are calcium ions important?
They aid with:
-muscle contraction
-enzyme activation
What does the release of DAG do?
Increases the levels of protein kinase C within the cell. This leads to the phosphorylation of enzymes and proteins.
What does phosphodiesterase do?
Breaks down cAMP
How is protein kinase A activated?
When cAMP binds to it
What enzyme breaks down acetylcholine?
acetylcholinesterase
What enzyme catalyses the formation of acetylcholine?
choline acetyltransferase
What effect does the influx of calcium ions in the presynaptic neurone have on the vesicles?
It causes vesicles containing acetylcholine to fuse with membrane
How is choline transported into the neurone?
By energy and sodium-dependent transporters
What does an influx of sodium ions into the neurone do?
Depolarises it (activates)
Describe what happens when choline and sodium ions are transported in to the neurone? (very detailed)
- Choline binds with acetyl Coenzyme A to form acetylcholine; this is catalysed by cholineltransferase
- Acetylcholine is transported into a presynaptic vesicle
- Movement of sodium ions causes the action potential of the neurone to change, which then stimulates the opening of voltage-sensitive calcium channels to open
-The influx of calcium ions into the neurone causes the fusion of the presynaptic vesicles with the membrane, releasing acetylcholine
- Acetylcholine then binds to the postsynaptic receptor, which leads to a cholinergic response. It also binds to the presynaptic neurone receptorinhibiting the release of more acetylcholine into the synaptic cleft
-Acetylcholinesterase inhibits acetylcholine function by breaking it down into choline (taken back into the neurone) and acetate.
What do the presynaptic vesicles prevent from happening to acetylcholine?
Degradation
What are the two types of cholinergic receptors?
nicotinic and muscarinic
What does double inhibition lead to?
excitation
What is GABA?
inhibitory neurotransmitter
