2.1 Intracellular Signalling Pathways

Question 1

What is signal transduction?

Answer 1

1. Signalling molecule activates specific receptor

2. Triggers chain of biochemical events inside cell

Question 2

What is the difference between an agonist and antagonist?

Answer 2

1. Agonists
   - bind to receptor and activate it
   - lead to intracellular signal transduction events
   - posses affinity (how well a ligand binds to receptor)and efficacy (how much of a response you get)
2. Antagonists
   - bind to a receptor but do not activate it
   - blocks effects of agonists at receptor
   - high affinity, no efficacy

Question 3

What do GPCRs respond to?

Answer 3

1. Sensory -light,odours,taste
2. ions
3. NT
4. peptide/non-peptide hormones
5. large glycoproteins

Question 4

What are the 3 superfamilies of CELL-SURFACE receptor?

Answer 4

1. Kinase linked
2. Ionotropic
3. NOT NUCLEAR/INTRACELLULAR CUZ NOT CELL SURFACE
4. G protein coupled receptors

KING - N

Question 5

What is the structure of a GPCR? What determines the size of it?

Answer 5

1. Single polypeptide chain
2. 7 transmembrane spanning regions
3. Extracellular N region
4. Intracellular C terminal

Size determined by size of N and C terminals

Question 6

Where does ligand binding occur on GPCR? What does a ligand binding cause?

Answer 6

1. Some receptors binding site buries in middle of TM proteins 2 an 3
2. For other receptors, bind to N terminal

Cause a change of conformation switching it from off to on

Question 7

List the stages of G protein effector signalling.

Answer 7

All happening on inner face of plasma membrane

1. Ligand binds, GPCR changes conformation, switches on
2. Activated GPCR interacts with G protein (GDP+ALPHA+BETA GAMMA)
3. GTP swaps with GDP on G protein (GTP+ALPHA+BETA GAMMA)
4. ALPHA-BETA GAMMA complex immediately dissociates as alpha loses affinity for BETA GAMMA
5. Each can go on and interact with effector proteins

Question 8

List the steps that occur when GPCR signalling is being terminated?

Answer 8

1. We currently have ALPHA-GTP.
2. ALPHA unit possesses intrinsic GTPase
3. GTPase hydrolyses GTP to GDP now we have ALPHA-GDP
4. ALPHA-GDP immediately regains affinity for BETA GAMMA complex
5. Back to inactive state

Question 9

The alpha unit possesses a poor GTP-ase. What effect does this have?

Answer 9

Hydrolyses GTP slowly so gives time for dissociated components to pass on signals

Question 10

Toxins can have an affect on GPCR systems. How does cholera work?

Answer 10

1. Systematically modifies all Galpha,s, containing proteins
2. They are now unable to hydrolyse GTP to GDP
3. Permanently in an on state as doesn’t recover affinity for BETA GAMMA

Question 11

Toxins can have an affect on GPCR systems. How does pertussis work?

Answer 11

1. Interacts with G,alpha,i protein by covalently modifying

2. Stops GDP swapping for GTP and so can’t be turned on as ALPHA subunit doesn’t lose affinity for BETA GAMMA