3 - G-Protein Coupled Receptors (GPCRs) I

Question 1

What are GPCRs also known as?

Answer 1

Metabotropic receptors.

Question 2

What are some structural features of GPCRs?

Answer 2

• 7 transmembrane domains.
• TM3 is located centrally next to the binding pocket, crucial for transduction of ligand binding.

Question 3

What are protease activated receptors (PARs) in platelets?

Answer 3

Receptors activated by the cleavage of N-Terminal which acts as a tethered ligand, part of the receptor itself acts as the agonist.

Question 4

What are G-Proteins?

Answer 4

• Guanine nucleotide binding proteins (GTPase family)
• They act as molecular switches inside cells to transmit signals from extracellular stimuli
• They are regulated by the ability to bind and hydrolyse GTP to GDP.

Question 5

What is the basic mechanism of GPCRs?

Answer 5

• The a-subunit in its resting state is bound to GDP
• When the receptor is occupied the GDP is displaced with GTP which activates the G-protein.
• When the a-subunit is activated it dissociates from the membrane and also from the other 2 subunits.
• This results in 3 active components.

Question 6

What is the duration of G-protein signalling regulated by?

Answer 6

The rate of GDP hydrolysis by Ga.

Question 7

What stimulates GTPase activity in the a-subunit?

Answer 7

RGS (Regulators of G-protein signalling) proteins.

Question 8

What determines the response of a G protein?

Answer 8

The specific subunit and cell type eg. The golf-a subunit to detect smell.

Question 9

How are G-Proteins controlled?

Answer 9

1) by direct activation of an ion channel, similar to how a ligand gated ion channel works.
2) Activated G-Proteins regulate the activities of enzymes that control the levels of second messengers.

Question 10

Why are second messenger systems needed?

Answer 10

Because a ligand binging to GPCR results in the phosphorylation (activation) of millions of proteins, which could lead to bacterial infections when it goes wrong.

Question 11

What are some bacterial infections that can come from ligand binding to GPCRs?

Answer 11

Cholera Toxin and whooping cough.

Question 12

Cholera Toxin

Answer 12

• Caused by the bacterium vibrio cholera
• G protein is a Gs a-subunit
• The 2nd messenger activates adenylate cyclase which catalyses cAMP to activate protein kinases
• Causes an increase in chloride ion, sodium ion and water secretion.
• Results in excess fluids and electrolytes in the lumen of the small intestine.