ICPP 10 - Signal Transduction

Question 1

What are the 3 “superfamilies” of cell surface receptors?

Answer 1

1) GPCR’s
2) Ligand gated ion channels (ionotropic receptors)
3) Receptors with intrinsic enzyme activity e.g.: tyrosine kinase receptors

Question 2

Describe the difference between ligand agonists and antagonists.

Answer 2

Agonists = bind to produce a biological effects
Antagonists = bind but dont activate, simply block the effects of the agonists.

Question 3

What is the common basic structure of a GPCR?

Answer 3

7TM domains as a single polypeptide chain (300-1200 AA’s) with an extracellular N-terminus and an intracellular C-terminus.

Question 4

Where are the 2 regions of binding for ligands in GPCR’s?

Answer 4

1) In between TM domains 2&3 (most common)

2) Extracellular domains within the N-terminus

Question 5

What occurs in the GPCR after ligand binding?

Answer 5

• Conformational change in G-protein receptor
• Activation of G-protein, GDP on alpha subunit switched for GTP
• Dissociation of alpha (+GTP) and beta-gamma subunits, which interact with effector proteins

Question 6

How are G-protein signals terminated?

Answer 6

• GTPase hydrolyses GTP on alpha subunit back to GDP

- affinity of alpha subunit for beta-gamma subunit increases, they reform and go back into resting state

Question 7

What secondary messenger does Gs, Gi and Gq initially activate?

Answer 7

Gs = Adenylyl cyclase (stimulates)
Gi = Adenylyl cyclase (inhibits)
Gq = Phospholipase C (stimulates)

Question 8

How does pertussis (whooping cough) caused by Bordetella pertussis interfere with G-protein signalling?

Answer 8

Covalently modifies G-protein (Gi) such that GTP cannot be exchanged for GDP which means the G-protein cannot be activated.
- It uncouples Gi-preferring GPCR’s from mediating signal transduction events.

Question 9

How does Cholera, caused by vibrio cholerae interfere with G-protein signalling.

Answer 9

Prevents termination of signalling by Gs-preferring GPCR’s leading to long lasting activation of downstream pathways.