5 - G protein coupled receptors

Question 1

What are ionotropic receptors?

Answer 1

ligand-gated ion channels
direct exchange of ions through signal transduction pore in the ion channel

Question 2

What are metabotropic receptors?

Answer 2

indirectly linked to ion channels through signal transduction mechanisms

Question 3

What are the structural features of GPCRs?

Answer 3

• Characteristic 7 TMs (alpha helices) -packed in a similar way
• TM3 centrally located next to binding pocket - crucial for transduction of ligand binding

conformational change particularly in TM5+6
- opens up binding pocket

N-terminus - extracellular side (ligand binding)
C-terminus - intracellular side (G-protein binding)

Question 4

How are GPCR classes distinguished?

Answer 4

by structural features of the extracellular domains defining the ligand binding site
huge diversity of stimuli GPCRs can detect

Question 5

What are G proteins?

Answer 5

guanosine nucleotide binding proteins
belong to GTPase family
act as molecular switches inside cell - transmit sig from extracellular
exist at heterotrimeric complexes - made up of alpha, beta, gamma

Question 6

How are g proteins regulated?

Answer 6

regulated by ability to bind + hydrolyse GTP (on) to GDP (off)

Question 7

What is the basic mechanism of GPCRs?

Answer 7

Inactive state - GDP bound to alpha subunit
1. Ligand binding = conformational change in receptor
activates G-protein

2. GDP released
   alpha subunit separates from other subunits + binds to GTP - now active
3. Binds to target protein in the membrane - elicit response in cell

Question 8

How is G protein signalling controlled?

Answer 8

Duration of signalling regulated by rate of GDP hydrolysis to Galpha
RGS (regulators of G-protein signalling) proteins stimulate GTPase activity in alpha subunit