12. Introduction To Receptors

Question 1

What is signal transduction?

Answer 1

Many cells require transduction of initial ligand binding event via other intracellular signalling components to generate a response

Question 2

What is the structure of G-protein coupled receptors?

Answer 2

Single polypeptide chain
7 transmembrane spanning regions
Extracellular N-terminal
Intracellular C-terminal

Question 3

What are the 2 regions of GPCRs ligand can bind to?

Answer 3

Ligand binding site formed by the transmembrane domains

Ligand dining site formed from N-terminal region

Question 4

How do GPCRs respond to ligands?

Answer 4

Change 3D conformational shape

Activated GCPR facilitates the activation of intracellular proteins called G proteins

Question 5

What are G proteins?

Answer 5

Guanine nucleotide binding protein

Made up of 3 subunits - alpha, beta, gamma

Question 6

GCPR-G protein interaction

Answer 6

Activates G protein by causing GDP to exchange for GTP on the G protein alpha subunit
Alpha-betagamma complex immediate dissociates into alpha-GTP and free beta-gamma, each can interact with effector proteins
Continues until alpha subunit GTPase activity hydrolysed GTP back to GDP

Question 7

How does pertussis toxin work?

Answer 7

Uncoupled Gi-preferring GPCRs from mediating single transduction events
Prevents GTP replacing GDP on alpha subunit

Question 8

How does cholera toxin work?

Answer 8

Prevents termination of signalling by Gs-preferring GPCRs leading to long-lasting activation of downstream pathways
Prevents hydrolysed of GTP back to GDP so the interaction with effectors continue