Ligand binding: G-proteins

Question 1

What are the functions of G-proteins?

Answer 1

Act as molecular on/off switches in signalling pathways, sensory perception, vesicle transport, protein synthesis

Question 2

Is a G-protein bound to GTP active or inactive?

Answer 2

Active

Question 3

Is a G-protein bound to GDP active or inactive?

Answer 3

Inactive

Question 4

How do you activate a G-protein?

Answer 4

Switch GDP with GTP

Question 5

How do you inactivate a G-protein?

Answer 5

GTP-hydrolysis

Question 6

What are the 3 types of G-proteins?

Answer 6

Small, translation factors, heterotrimeric

Question 7

What are the 3 subunits of heterotrimeric G-proteins?

Answer 7

Alpha, beta and gamma

Question 8

What are G-protein coupled receptors (GPCRs)?

Answer 8

Integral membrane receptors that will change conformation and activate the associated G-protein when a signal binds

Question 9

What happens to the G protein when a signal binds to the GPCR?

Answer 9

GDP is switched with GTP and the protein activates. The beta and gamma subunits dissociate and the alpha stays at the membrane and is active

Question 10

What happens to a G-protein when GTP hydrolysis occurs?

Answer 10

The beta and gamma subunits return and form the trimer again

Question 11

What are the two domains in the G alpha subunit?

Answer 11

GTPase and helical

Question 12

What are the 4 regions in the G alpha subunit?

Answer 12

P-loop, Switch 1, switch 2, switch 3

Question 13

What is a P-loop?

Answer 13

A nucleotide binding motif where the GTP or GDP is bound

Question 14

What is the conserved consensus sequence in the P-loop?

Answer 14

GXGESGKS

Question 15

What does switch 1 do?

Answer 15

Flexible loop that creates contacts between the alpha and beta subunits

Question 16

What does switch 2 do?

Answer 16

Interacts with the gamma phosphate of GTP and releases the beta and gamma subunits, or interacts with the beta and gamma subunits when GDP is bound

Question 17

What does switch 3 do?

Answer 17

Flexible loop involved in receptor mediated activation

Question 18

What motif is present in the G beta subunit?

Answer 18

Beta propellor

Question 19

Which Switch loop undergoes the largest conformational change between the GTP bound and GDP bound states?

Answer 19

Switch 2

Question 20

What two things regulate the activation and inactivation of G-proteins?

Answer 20

GEFs and GAPs

Question 21

What do GEFs do?

Answer 21

Guanosine exchange factors. They switch GDP for GTP

Question 22

What do GAPs do?

Answer 22

GTPase activator proteins. They speed up the intrinsic GTPase activity

Question 23

How many human diseases are associated with defective G-proteins or GPCRs?

Answer 23

25%

Question 24

Why are defective G proteins involved in cancer and diabetes?

Answer 24

A mutation in a G protein involved in a cell division pathway will make it less likely to turn off, causing uncontrolled cell division

Question 25

What toxins will target G proteins? How do they affect G-proteins?

Answer 25

Cholera and pertussis. They covalently modify the alpha subunit and leave it permanently on

Question 26

What does bee and wasp venom do?

Answer 26

The peptides insert themselves in the membrane and mimic GPCRs. They activate G proteins