L10 G-protein receptor families

Question 1

G protein-coupled receptors: location

Answer 1

membrane
7 transmembrane domains

Question 2

G protein-coupled receptors: Effector

Answer 2

Enzyme or channel

Question 3

G protein-coupled receptors: respond to

Answer 3

Hormones or slow NT

Question 4

G protein-coupled receptors: TimeSOA

Answer 4

Fast
seconds

Question 5

G protein-coupled receptors: Examples

Answer 5

Adrenoceptors and muscarinic acetylcholine receptors

Question 6

Salbutamol is an agonist to what and does what

Answer 6

Salbutamol, a b2-adrenoceptor agonist relieves bronchospasm in asthma

Question 7

acetylcholine agonist to what to activate what

Answer 7

muscarinic acetylcholine receptors activate phospholipase C

Question 8

adrenaline agonist to what to activate what

Answer 8

ß-adrenoceptors activate adenylate cyclase;

Question 9

Structure of GPCR

Answer 9

• metabotropic receptors
• 7 transmembrane domain receptors heptahelical receptors
• heterotrimeric G protein
• Gas – activates adenylate cyclase (e.g., b2-adrenoceptor)
• Gai – inhibits adenylate cyclase (e.g., a2 adrenoceptor)
• Gaq – activates phospholipase C (e.g., muscarinic receptor)

Question 10

b2-Adrenoceptor structure

Answer 10

1. extracellular N-terminus
2. 7 transmembrane a-helices
3. 3 extracellular & 3 intracellular loops
4. intracellular C-terminal tail

Question 11

Protein phosphatases:

Answer 11

dephosphorylate proteins cause inactivation

Question 12

Protein kinases:

Answer 12

phosphorylate proteins cause activation

Question 13

The a-subunit binds what and has GTPase activity

Answer 13

GTP and has GTPase activity

Question 14

3 main classes of Ga protein

Answer 14

• Gas activates adenylate cyclase
• Gai inhibits adenylate cyclase
• Gaq activates phospholipase C

Question 15

G proteins link GPCRs to effector proteins that generate intracellular second messengers - what msg are generated

Answer 15

• (Gas) adenylate cyclase generates cAMP
• (Gaq) phospholipase C generates inositol 1,4,5-trisphosphate & diacylglycerol

Question 16

Adenylate cyclase signal transduction pathway

Answer 16

• Agonist activation → conformational change
• Affinity of receptor for G protein increases

Question 17

Activation of G protein

Answer 17

• Receptor binds to heterotrimeric G protein
• Binding → conformational change in Ga
• GTP binds to Ga
• Ga catalyses exchange of GDP for GTP

Question 18

Activation of adenylate cyclase enzyme

Answer 18

• Ga dissociates from G(bg)
• Ga binds to adenylate cyclase
• Adenylate cyclase → cyclisation of ATP to cAMP

Question 19

Inactivation of G protein

Answer 19

• GTP hydrolysed to GDP
• Ga dissociates from adenylate cyclase
• Ga binds to Gbg

Question 20

Receptor return to resting state

Answer 20

• Receptor dissociates from G protein
• G protein inactivated
• Agonist no longer binds to receptor
• Receptor returns to resting state

Question 21

ß2-Adrenoceptor signalling cascade

Answer 21

Adrenaline → ß2-adrenoceptor → G(as) → adenylate cyclase → cAMP → cAMP-dependant protein kinase A →relaxation

Question 22

Muscarinic acetylcholine receptor signalling cascade

Answer 22

acetylcholine → muscarinic acetylcholine receptor →G protein (Gaq)→ phospholipase C →IP3 or DAG→ Ca2+ or PKC →contraction