Signal Transduction 2: GPCR

Question 1

What are the major structural features of GPCRs

Answer 1

• 7 transmembrane alpha helices
• N terminal is on the extracellular side and the C terminal is on the intracellular side
• Helices joined by 3 intracellular and 3 extracellular loops.

Question 2

Describe the Gprotein cycle (5 steps)

Answer 2

1.In inactive form the G protein exists as a trimer, attached to GDP.
2. G protein binds to GPCR causing conformational change which allows G a-subunit to release the GDP and bind to GTP instead.
3. Ga subunit dissociates from GBy subunit
and now the Ga subunit is active and can effect effectors.
4. Ga subunit enzyme hydrolyses GTP back to GDP. (auto off switch).
5. Then Ga reassociate with GBy subunits to go back to inactive form.

Question 3

What are effector proteins in signal transduction,

Answer 3

Molecules (often enzymes) inside the cell that respond to a stimulus and can be activated and further transduce a signal. (receives a messenger)

Question 4

What is the structure of a G protein

Answer 4

It is a heterotrimer: 3 subunits. (a and By dimer) Subunits can dissociate from each other.

A- subunit can bind to GDP or GTP. (G protein binds to Guanine nucleotides.

Question 5

What allows G protein to bind to GPCR

Answer 5

G protein can bind to GPCR due to conformation change caused by ligand binding to receptor.

Question 6

Name the 3 different types of G protein

Answer 6

Gs (stimulatory)
Gi (inhibitory)
Gq (activates phospholipase C)

Question 7

What is the difference between Gs and Gi (Gas and Gai) and the resulting cAMP conc in cell.

Answer 7

Ga favours catalytically active form of adenylate cyclase which makes ATP-> cAMP

whereas Gi favours catalytically inactive form of adenylate cyclase so decreases cAMP conc in cell.

Question 8

What effector does cAMP effect

Answer 8

Cyclic AMP activates Protein kinase A which starts a phosphorylation pathway.

Question 9

What does Gaq (Gq) effect and how

Answer 9

1. Once active, Gaq will act on Phospholipase C on the membrane.
2. PLC converts PIP2 into DAG and IP3.
3. IP3 releases Ca2+ from the ER which allows DAG to activate protein kinase C
4. Protein kinase C goes on to phosphorylate downstream events

Question 10

What does Gaq (Gq) effect and how

Answer 10

1. Once active, Gaq will act on Phospholipase C on the membrane.
2. PLC converts PIP2 into DAG (stays in membrane) and IP3.
3. IP3 releases Ca2+ from the ER which allows DAG to activate protein kinase C
4. Protein kinase C goes on to phosphorylate downstream events