G-protein Coupled Receptors

Question 1

When an agonist binds to its receptor, what is formed?

Answer 1

A drug-receptor (D-R) complex

Question 2

Triggers a biological response, what is this process?

Answer 2

Signal transduction

Question 3

List the 3 stages of the receptor signalling process

Answer 3

• Signal reception (agonist drug binds to & activates receptor)
• Signal transduction (produces 2nd messengers inside cell)
• Cellular response (biological response signal triggered)

Question 4

List the 4 major signal transduction pathways

Answer 4

• Activation of receptor-ion channels (Ligand-gated)
• Activation of second messenger pathways (GPCRs)
• Activation of enzyme-linked receptors (kinase-linked)
• Direct activation of gene transcription via intracellular receptors

Question 5

What is the timescale for each receptor superfamily?

Answer 5

• Ligand-gated: milliseconds (nicotinic)
• GPCRs: seconds (muscarinic)
• Kinase-linked: hours (cytokine)
• Nuclear: hours (oestrogen)

Question 6

What do GPCRs convert?

Answer 6

Convert extracellular signals into intracellular responses

Question 7

What structure do GPCRs share?

Answer 7

7-TM a-helices

Question 8

What does a GPCR consist of?

Answer 8

• Extracellular region: N terminus & 3 extracellular loops (ECL1-3)
• TM region: 7TM a-helices
• Intracellular region: ICL 1-3

Question 9

What are heterotrimeric G-proteins composed of?

Answer 9

a, B and y

Two subunits: a subunit (Ga) and a tightly associated By complex

Question 10

What 2 domains is the Ga subunit composed of?

Answer 10

• Ras-like domain

- a-helical domain

Question 11

What is located between the 2 domains of the Ga?

Answer 11

A nucleotide-binding pocket

Question 12

How are G-proteins classified?

Answer 12

Based on their Ga subunits

Question 13

List the 4 Ga families

Answer 13

1) Gas - stimulate adenylate cyclase
2) Gai - inhibit adenylate cyclase
3) Gaq/11 - stimulate phospholipase
4) Ga12/13 - activate the Rho family of GTPases

Question 14

Most Ga proteins mediate GPCR signalling by regulating the levels of intracellular regulatory molecules called ______

Answer 14

second messengers

Question 15

Adenylyl cyclase (AC) converts _____ to _____

____ stimulates this activation of AC

Answer 15

ATP
cAMP

Gas-GTP

Question 16

Increased cAMP level leads to activation of ____

Answer 16

protein kinase A (PKA)

Question 17

Gaq/11-GTP activates PLCB in ______

Answer 17

cell membrane

Question 18

Activated phospholipase C-B (PLCB) generate 2nd messengers
__________
__________

Answer 18

Inositol triphosphate (IP3)
Diacylglycerol (DAG)

Question 19

IP3 diffuses through cytosol and releases _____ from ER

Answer 19

Ca2+

Question 20

DAG activates_______

Answer 20

protein kinase C

Question 21

GB & Gy form ______

Answer 21

obligate functional heterodimer

Question 22

Temporal & spatial signalling of activated GPCRs is controlled by _____ & _______

Answer 22

Desensitisation

Internalisation

Question 23

What 2 major intracellular actors does this trafficking require?

Answer 23

• G-protein coupled receptor kinases (GRKs)

- B-arrestins (cytoplasmic adaptor proteins)

Question 24

What do B-arrestins facilitate?

Answer 24

Receptor internalisation

Question 25

What are the 3 possible fates when GPCRs are trafficked to endosomes?

Answer 25

• May be dephosphorylated by phosphates & recycle back to cell surface for future signalling
• May be sorted to lysosomes for degradation
• May activate B-arrestin & G-protein independent signalling

Question 26

What do B-arrestins couple the phorphorylated GPCRs to?

Answer 26

clathrin-coated pits