GPCRs

Question 1

What is signal transduction?

Answer 1

The transformation of the initial ligand binding event via intracellular signalling components to generate a response

Question 2

What is signal amplification?

Answer 2

Refers to how the initial ligand binding event starts off a signalling cascade
where one molecule activates many molecules in turn
produces a relatively massive cellular response

Question 3

What are some examples of stimuli that GPCRs resond to?

Answer 3

Light, odours, tastes

Ions

Neurotransmitters

Hormones

Question 4

What is the basic structure of a GPCR?

Answer 4

Single polypeptide chain
7 transmembrane regions
N-terminus is extracellular
C-terminus is intracellular

Question 5

Where on a GPCR can a ligand bind to it?

Answer 5

A few of the transmembrane regions

N-terminal region

Question 6

What is the structure of a G-protein?

Answer 6

Heterotrimeric, meaning it has three different subunits

• alpha
• beta
• gamma

Question 7

What is the alpha subunit in a G-protein bound to?

Answer 7

GDP/GTP

Question 8

What are the beta and gamma subunits in a G-protein bound to?

Answer 8

Bound to each other

Question 9

What happens to a GPCR when a ligand binds to it?

Answer 9

It changes conformation

Question 10

What happens to the G-protein when a ligand binds to the GPCR?

Answer 10

GTP replaces GDP on the alpha subunit

this causes the beta-gamma subunit to dissociate from the alpha subunit

Question 11

What do the free alpha and beta-gamma subunits do?

Answer 11

Interact with effector proteins

Question 12

What are some examples of the types of effector proteins?

Answer 12

Enzymes that generate second messengers

Ion channels

Question 13

How is GPCR signalling terminated?

Answer 13

Alpha subunit has intrinsic GTPase
hydrolysis GTP on alpha subunit to GDP
alpha and beta-gamma subunits rejoin

Question 14

How do GPCRs produce specific responses?

Answer 14

Specific ligand binds to specific GPCR
interacts with specific G-protein
alpha and beta-gamma subunits interact with specific effector proteins

Question 15

What are the different ligands that bind to GPCRs?

Answer 15

Adrenaline, noradrenaline

Acetylcholine

Question 16

What are the different types of GPCRs?

Answer 16

Alpha1

Alpha2

Beta1

Beta2

Muscarinic1

Muscarinic2

Muscarinic3

Question 17

What are the different types of G-proteins?

Answer 17

G-alpha-s

G-alpha-i

G-alpha-q

Question 18

What are the different types of G-proteins based on?

Answer 18

The alpha subunit

Question 19

What does the free alpha-s subunit do?

Answer 19

Stimulates adenylyl cyclase

Question 20

What does the free alpha-i subunit do?

Answer 20

Inhibits adenylyl cyclase

Question 21

What does the free alpha-q subunit do?

Answer 21

Stimulates phospholipase C

Question 22

What does adenylyl cyclase do?

Answer 22

Catalyses the reaction

ATP —–> cAMP

Question 23

What is the structure of PKA?

Answer 23

Two regulatory subunits
Two catalytic subunits

Catalytic subunits are bound to by the regulatory subunits

Question 24

What does cAMP do?

Answer 24

Four cAMP molecules bind to the regulatory subunits of PKA - two cAMPs per regulatory subunit

Question 25

What does cAMP binding to the regulatory subunits of PKA do?

Answer 25

Causes the regulatory subunits to release the catalytic subunits catalytic subunits are free

Question 26

What do the free catalytic subunits of PKA do?

Answer 26

Phosphorylate target proteins in the cell

Question 27

What does phospholipase C do?

Answer 27

Catalyses the reaction | PIP2 -----> IP3 + DAG

Question 28

What is PIP2? Where is it found in a cell?

Answer 28

A phospholipid | located in the plasma membrane

Question 29

What does IP3 do?

Answer 29

Binds to IP3 receptors on the endoplasmic reticulum

Question 30

What does IP3 binding to IP3 receptors do?

Answer 30

Causes the ligand-gated ion channel to open | and calcium to be released into the cytoplasm

Question 31

What does the raised cytoplasmic calcium concentration result in?

Answer 31

Activation of PKC

Question 32

What does DAG do?

Answer 32

Activates PKC

Question 33

Which types of GPCRs do adrenaline and noradrenaline bind to?

Answer 33

A1 A2 B1 B2

Question 34

Which types of GPCRs does acetylcholine bind to?

Answer 34

M1 M2 M3

Question 35

What type of G-protein is the A1 GPCR coupled to?

Answer 35

Gq

Question 36

What type of G-protein is the A2 GPCR coupled to?

Answer 36

Gi

Question 37

What type of G-protein are the B1 and B2 GPCRs coupled do?

Answer 37

Gs

Question 38

What type of G-protein is the M1 GPCR coupled to?

Answer 38

Gq

Question 39

What type of G-protein is the M2 GPCR coupled to?

Answer 39

Gi

Question 40

What type of G-protein is the M3 GPCR coupled to?

Answer 40

Gq

Question 41

What are two examples of toxins that affect GPCR function?

Answer 41

Cholera toxin Pertussis toxin

Question 42

What type of G-protein does the cholera toxin affect?

Answer 42

Gs

Question 43

How does the cholera toxin affect Gs proteins?

Answer 43

Inhibits GTPase on alpha subunit

Question 44

What type of G-protein does the pertussis toxin affect?

Answer 44

Gi

Question 45

How does the pertussis toxin affect Gi proteins?

Answer 45

Prevents GTP replacing GDP on the alpha subunit