ICPP S3 Receptor Effector Mechanism

Question 1

What are the 3 superfamilies of cell-surface receptor?

Answer 1

GPCRs

LGICs

Receptors with intrinsic enzymatic activity - Tyrosine kinase for example.

Question 2

What is the basic structure of a GPCR?

Answer 2

Single polypeptide chain (300-1200AAs)
7 transmembrane domains
Extracellular N terminus
Intracellular C terminus

Question 3

What antagonists can be used to treat hypertension?

Answer 3

Propranolol and atenolol

Question 4

What antagonists can be used as neuroleptics ie anti-schizophrenics?

Answer 4

Haloperidol, sulpride.

Question 5

What agonists are used to treat asthma?

Answer 5

Salbutamol, salmeterol

Question 6

What agonists are used as analgesics and anaesthetics?

Answer 6

Morphine, fentanyl

Question 7

What stimuli can GPCRs respond to?

Answer 7

Ions
NTs
Large glycoproteins
Peptide and non-peptide hormones

Question 8

What are 2 ways in which a ligand can interact and bind to a GPCR?

Answer 8

Bind to a site formed by 2-3 of the TM domains.

Bind straight onto extracellular N terminus.

Question 9

What does G protein stand for?

Answer 9

Guanine nucleotide-binding protein

Question 10

GPCRs activate what?

Answer 10

G proteins

Question 11

State the role of G-proteins.

Answer 11

Transducers

Question 12

What is the basic structure of a G protein?

Answer 12

3 subunits - alpha, beta and gamma
Beta, gamma in close association
Heterotrimeric

Question 13

When a ligand binds to a GPCR, how does this end up with the effector being signalled?

Answer 13

Binding of ligand with GPCR changes its conformation.
Increases interaction of GPCR with G-protein.
Increased interaction causes GDP on the alpha subunit to be transferred for GTP.
This transfer reduces affinity between the alpha and beta-gamma subunits and causes dissociation of the subunits.
alpha and beta-gamma subunits can interact with their relevant effector proteins.

Question 14

How is termination of the G-protein signal achieved?

Answer 14

Alpha-GTP and beta-gamma sub-units interact with effectors until the alpha subunit’s GTPase activity increases.
Increase in the GTPase activity causes hydrolysis of GTP back to GDP and subsequently increases the affinity between the alpha and beta-gamma subunits.
Reform their inactive heterotrimeric state.

Question 15

In terms of the G-proteins, how many sub-units are encoded by the human genome?

Answer 15

20 alpha
5 beta
12+ gamma

Question 16

What is the primary determinant of preferential G protein and GPCR interaction?

Answer 16

The alpha subunit.

Question 17

Make sense of the pneumonic QISS QIQ SIQ SQS.

Answer 17

A1-q
A2- i
B1- s
B2- s

M1-q
M2-i
M3-q

D1-s
D2-i
H1-q

H2-s
V1-q
V2-s

Question 18

What are Gs effectors?

Answer 18

+ Adenylyl cyclase

Question 19

What are Gi effectors?

Answer 19

• Adenylyl cyclase

- VOCCs

Question 20

What are Gq effectors?

Answer 20

+ Phospholipase C

Question 21

Which bacterium causes pertussis?

Answer 21

Boredetella pertussis.

Question 22

What toxins does Boredetella pertussis release?

Answer 22

PTx

Question 23

What effect does PTx have on G-protein function?

Answer 23

Uncoupling Gi preferring GPCRs - stopping signal transduction.

Covalently modifies alpha subunit, inhibiting ability to undergo GTP for GDP transfer.

Question 24

What is cholera and what are it’s symptoms?

Answer 24

Infection of the small intestine

Watery diarrhoea
Vomiting
Cramps

Question 25

What bacterium causes cholera?

Answer 25

Vibrio cholerae

Question 26

What toxin does Vibrio cholerae release?

Answer 26

CTx

Question 27

What the effect of toxin CTx on G-protein function?

Answer 27

Prevents termination of Gs preferring pathways. Leads to long lasting activation of pathways.
CTx covalently modifies alpha subunit, arresting its GTPase activity.
Continued signalling will occur and cAMP levels will rise.