GPCRs

Question 1

How many different familes of GPCRs are there?

Answer 1

4: Gi, Gs, Gq and G12/13

Question 2

How many different subfamilies of GPCRs are there?

Answer 2

5: Rhodopsin, Adhesin, Secretin, Glutamate and Frizzled (or A-E)

Question 3

Describe the general topology of a GPCR.

Answer 3

Monomer (some are dimers, most family C GPCRs), with 7 TMs, extracellular N-terminal, intracellular C-terminal. Binding pocket in the middel of the circle of TMs, but mainly TM3, -5 and -6 are involved.

Question 4

How is a G-protein activated?

Answer 4

The GDP on the alpha-subunit is replaced by a GTP, and the alpha-subunit diasociates from the beta-gamma-subunit.

Question 5

How is a G-protein inactivated.

Answer 5

Bound GTP is hydrolyzed into GDP.

Question 6

What are GRKs?

Answer 6

G-protein-linked receptor kinase. GRKs phosphorylate the activated GPCR, which allows arrestins to bind to the phosphorylated sites, inhibiting the GPCR. GRKs are activated by G-alpha and G-beta-gamma. GRK also hydrolyse GTP to GDP on the G-alpha-subunit.

Question 7

Describe the function of cholera.

Answer 7

Block Gs in the active state leading to continued activation of AC, which dramatically increases cAMP conc., resulting in decreased Na^+ absorption and increased Cl^- secretion by crypt cells. This leads to a dramatic water loss through the gut lumen.