GPCRs

Question 1

What are GPCRs coupled to?

Answer 1

G-proteins

Question 2

How do GPCRs cause signalling cascades?

Answer 2

• Receptor binds to ligand and induces conformational change
• Cytoplasmic face can now couple to G proteins and causes G proteins to take on GTP
• This changes their conformation and activates them causing enzymatic activities

Question 3

Which subunit of the heterotrimeric G proteins has intrinsic GTPase activity?

Answer 3

Alpha

Question 4

What occurs after GPCR activation to allow for GTP binding in the heteromeric G-protein?

Answer 4

• TM6 moves and opens up a hole for binding of the alpha subunit
• The alpha5 of G-alpha subunit binds into the hole
• Movement of alpha5 helix induces opening of alpha subunit and allows for GDP displacement

Question 5

What is the function of Gαs proteins?

Answer 5

Stimulate adenyly cyclase leading to formation of cAMP

Question 6

Elevation in cAMP levels leads to activation of what?

Answer 6

PKA

Question 7

How does cAMP activate PKA?

Answer 7

PKA is attached to a regulatory subunit, when cAMP is added it binds to the regulatory subunit which causes the release of the active catalytic subunits

Question 8

How does signal amplification work in phototransduction in rhodopsin?

Answer 8

• Light causes a conformational change in GPCR
• Activation causes cation channels to close, causing depolarisation and transmitter release

Question 9

What is the function of arrestins?

Answer 9

They bind to GPCR and drive internalisation of GPCR from surface to endosome which restricts GPCR levels at cell surface

Question 10

When can arrestins bind to GPCRs?

Answer 10

When GPCRs have been phosphorylated