Topic 2: G-protein dependent signalling

Question 1

what moolecuels can modualte G-protin signalling

Answer 1

AGS- Activators of G-protein signalling
RGS- Regulators of G-protein signalling

Question 2

What are some families of GTPases

Answer 2

Small- Ras, Rac, Rho
Large - dynamin
translatonal- eIF2
Hetrotrimeric - G- proteins.

Question 3

what three subunits are hetrotrimeric G-proteins made of, what are their functions?

Answer 3

A
b
g
they are fuctionally dimeric
A subunit is fore
receptor recognition
effctor recognistion
GTP/GDP binding / GTPase activity
interaction with regulatory protiens.
the By subunit is responsible for Recptor recognition, GDP-bound A-subunint recognition
effector recognition.

Question 4

what are the key steps in the G-protein cycle

Answer 4

GDP-bound form of G-protein is hetrotimeric and inactive
Agonist bound GPCR acts as a GEF to promote GFP for GTP exchange.(GDP unbinding from Ga and GTP binding instead)
Ga- gtp bound diassaitates from Gby
termination by the intrinsic GTPase activaity of the G-protein
Ga-GDP rapidly reassoaites with Gby subunit.

Question 5

What does AlF-4 do in the presence of G-proteins

Answer 5

mimics GTP occupancy of the Ga sunbunit.

Question 6

what is an example of a non-hydroliseable form of GTP

Answer 6

GTPyS

Question 7

what does Pertussis toxin do to Gai/o

Answer 7

covalently modifys it so it is inhibited from being able to undergo GDP- for GTP exchange- lock in off state

Question 8

what does cholera toxin do to Gas

Answer 8

covalently modifies it so it cannot hydrolsise GTP so it is locked on.

Question 9

How do RGS proteins work?

Answer 9

they accllerate the intrinsci GTPase activation of the Ga sunbunit, quicker off times.

Question 10

some RGS-like domains (RH domains) ineracat with G-preotins but do not increase GTPase activity what do they do?

Answer 10

they may act as scaffolding proteins.

Question 11

How do GIRKs function?

Answer 11

in heart- M2 muscrinic activated to regulate griks
if there are no RGS4 proteins then slow inactivation and activation is seen

Question 12

what is an example of RGS proteins in action?

Answer 12

RGS9-1 is needed for normal photoreceptor responses to light
know out shows delays in recovery from photobleaching.

Question 13

RGS proteins interact with Ga what else can they interact with

Answer 13

also receptor-G-protein depenedent
as same RGS will have diffrent rates of inhibton depending on hwat GPCR the G-protein is bound to

Question 14

what are the roles of RGS proteins with a non catalytic RH domain?

Answer 14

p115rho/GEF it is a scaffolding protein- it binds to Ga13-GTP ands allows for GEF activity for Rho.