G protein coupled receptors

Question 1

G-protein coupled receptors

Answer 1

Largest receptor superfamily
Interact with heterotrimeric G proteins
* GTP- and GDP-binding proteins
Activate signal transduction pathways - adenylate cyclase, phospholipase C, phosphodiesterase, ion channels

Produces cascade affect

Question 2

G-protein coupled receptor as a drug target

Answer 2

targeted by neurotransmitters, hormones, opioids, amines, peptides, proteins, light-sensitive compounds, odours

Question 3

Describe the structure of G protein-coupled receptors

Answer 3

Metabotropic

N terminus is extra-cellular
C terminus is intra-cellular

Two ligand binding sites

Made of three different (heterotrimeric) subunits - Alpha, Beta and Gamma

7 Transmembrane spanning domains

Question 4

the role of G protein-coupled receptors in
physiological processes

Answer 4

• change membrane excitability (ion)
• generation of second messengers
• protein phosphorylation

Question 5

Example of G-protein receptor physiological role in body

Answer 5

In the ANS
Agonist: Acetylcholine
Receptor/effector: muscarinic acetylcholine receptors activate
phospholipase C

Question 6

Ga protein

Answer 6

Alpha subunit
- binds GTP and has GTPase activity
- 3 main classes of subunits
* Gas activates adenylate cyclase
* Gai inhibits adenylate cyclase
* Gaq activates phospholipase C

Question 7

G Protein

Answer 7

link GPCRs to effector proteins that generate intracellular second messengers
E.g.
* (Gas) adenylate cyclase generates cAMP
* (Gaq) phospholipase C generates inositol 1,4,5-trisphosphate & diacylglycerol

Question 8

Activation of G-protein

Answer 8

Agonist binds to receptor causing conformational change

Receptor affinity for G-protein increases –> Receptor binds to G-protein

Binding causes conformational change to Ga –> which catalyses the exchange of GDP to GTP allowing GTP to bind to Ga

Question 9

Activation of adenylate cyclase

Answer 9

Ga dissociates from Gby and binds to adenylate cyclase activating it

Active Adenylate cyclase converts ATP to cAMP

Question 10

Inactivation of G-protein

Answer 10

Ga hydrolyses GTP to GDP and dissociates from Adenylate cyclase

Reforms with Gby

Question 11

Return to resting state

Answer 11

Receptor dissociates from G-protein –> G-protein is inactivated

Agonist no longer binds to receptor, returning receptor to its resting state

Question 12

Adenylate cyclase signal transduction pathway

Answer 12

1. Ligand
2. receptor
3. Gas
4. Adenylate cyclase
5. ATP–> cAMP
6. cAMP dependant protein kinase A
7. response

Question 13

Beta-2 adrenoceptor signalling cascade

Answer 13

1. Adrenaline
2. binds to B2- receptor (airway smooth muscle) and activates it
3. G-protein binds to receptor (Gas)
4. Ga activates adenylate cyclase
   5.Adenylate cyclase converts ATP to cAMP
5. cAMP activates cAMP dependant kinase A
6. Relaxation

Question 14

Phospholipase C signal transduction pathway

Answer 14

1. Agonist binds to receptor
2. receptor binds to G-protein (Gaq)
3. Gaq activation binds to effector (phospholipase C)
4. Phospholipase C generates Inositol 1,4,5- trisphosphate and Diacylglycerol
5. IP3 releases calcium from the cytoplasmic retic binding to Calmodulin and DAG activates protein kinase C
6. response

Question 15

Muscarinic acetylcholine receptor signalling cascade

Answer 15

1. Acetylcholine
2. binds to Muscarinic acetylcholine receptor
   3.. receptor binds to G-protein (Gaq)
   4.. Gaq activation binds to effector (phospholipase C)
3. Phospholipase C generates Inositol 1,4,5- trisphosphate and Diacylglycerol
   6.. IP3 releases calcium from the cytoplasmic retic binding to Calmodulin and DAG activates protein kinase C
4. Contraction