7.1 Receptor-effector signalling via G-protein

Question 1

How does whooping cough take action?

Answer 1

blocks ADP-ribosyltransferase
so a-subunit can’t uncouple from ß & gamma
can’t activate to phosphorylate other substances
(heterodimer can’t come apart)

Question 2

How does cholera take action?

Answer 2

contains ADP-ribotransferase specific for Gs
inhibits GTPase - preventing hydrolysis of GTP –> GDP
so continue signalling of a-subunit, can’t recombine with ß & gamma

Question 3

Describe the signalling cascade consisting of 3 fundamental components: a receptor, a guanine nucleotide binding protein (or G protein) & an effector molecule, which may be an enzyme (e.g. adenylate cyclase) or an ion channel

Answer 3

G protein: heteromeric (alpha, beta, gamma), at basal conditions, GDP bound to alpha subunit (high affinity for G protein)

1. agonist bind & activate receptor
2. activated receptor: releases GDP & GTP binds to alpha subunit
3. this decreases affinity of alpha subunit with B & gamma
4. alpha-GTP releases to interact with effectors (e.g. adenylate cyclase –> ATP –> cAMP –> PKA)
5. interactions with effectors terminate by INTRINSIC GTPase WITHIN a-subunit (GTP –> GDP) hydrolysed)
6. affinity of a-subunit with beta & gamma now increases, reforms heterodimer