GPCRs Flashcards
What is signal transduction?
The transformation of the initial ligand binding event via intracellular signalling components to generate a response
What is signal amplification?
Refers to how the initial ligand binding event starts off a signalling cascade
where one molecule activates many molecules in turn
produces a relatively massive cellular response
What are some examples of stimuli that GPCRs resond to?
Light, odours, tastes
Ions
Neurotransmitters
Hormones
What is the basic structure of a GPCR?
Single polypeptide chain
7 transmembrane regions
N-terminus is extracellular
C-terminus is intracellular
Where on a GPCR can a ligand bind to it?
A few of the transmembrane regions
N-terminal region
What is the structure of a G-protein?
Heterotrimeric, meaning it has three different subunits
- alpha
- beta
- gamma
What is the alpha subunit in a G-protein bound to?
GDP/GTP
What are the beta and gamma subunits in a G-protein bound to?
Bound to each other
What happens to a GPCR when a ligand binds to it?
It changes conformation
What happens to the G-protein when a ligand binds to the GPCR?
GTP replaces GDP on the alpha subunit
this causes the beta-gamma subunit to dissociate from the alpha subunit
What do the free alpha and beta-gamma subunits do?
Interact with effector proteins
What are some examples of the types of effector proteins?
Enzymes that generate second messengers
Ion channels
How is GPCR signalling terminated?
Alpha subunit has intrinsic GTPase
hydrolysis GTP on alpha subunit to GDP
alpha and beta-gamma subunits rejoin
How do GPCRs produce specific responses?
Specific ligand binds to specific GPCR
interacts with specific G-protein
alpha and beta-gamma subunits interact with specific effector proteins
What are the different ligands that bind to GPCRs?
Adrenaline, noradrenaline
Acetylcholine
What are the different types of GPCRs?
Alpha1
Alpha2
Beta1
Beta2
Muscarinic1
Muscarinic2
Muscarinic3
What are the different types of G-proteins?
G-alpha-s
G-alpha-i
G-alpha-q
What are the different types of G-proteins based on?
The alpha subunit
What does the free alpha-s subunit do?
Stimulates adenylyl cyclase
What does the free alpha-i subunit do?
Inhibits adenylyl cyclase
What does the free alpha-q subunit do?
Stimulates phospholipase C
What does adenylyl cyclase do?
Catalyses the reaction
ATP —–> cAMP
What is the structure of PKA?
Two regulatory subunits
Two catalytic subunits
Catalytic subunits are bound to by the regulatory subunits
What does cAMP do?
Four cAMP molecules bind to the regulatory subunits of PKA - two cAMPs per regulatory subunit
What does cAMP binding to the regulatory subunits of PKA do?
Causes the regulatory subunits to release the catalytic subunits
catalytic subunits are free
What do the free catalytic subunits of PKA do?
Phosphorylate target proteins in the cell
What does phospholipase C do?
Catalyses the reaction
PIP2 —–> IP3 + DAG
What is PIP2? Where is it found in a cell?
A phospholipid
located in the plasma membrane
What does IP3 do?
Binds to IP3 receptors on the endoplasmic reticulum
What does IP3 binding to IP3 receptors do?
Causes the ligand-gated ion channel to open
and calcium to be released into the cytoplasm
What does the raised cytoplasmic calcium concentration result in?
Activation of PKC
What does DAG do?
Activates PKC
Which types of GPCRs do adrenaline and noradrenaline bind to?
A1
A2
B1
B2
Which types of GPCRs does acetylcholine bind to?
M1
M2
M3
What type of G-protein is the A1 GPCR coupled to?
Gq
What type of G-protein is the A2 GPCR coupled to?
Gi
What type of G-protein are the B1 and B2 GPCRs coupled do?
Gs
What type of G-protein is the M1 GPCR coupled to?
Gq
What type of G-protein is the M2 GPCR coupled to?
Gi
What type of G-protein is the M3 GPCR coupled to?
Gq
What are two examples of toxins that affect GPCR function?
Cholera toxin
Pertussis toxin
What type of G-protein does the cholera toxin affect?
Gs
How does the cholera toxin affect Gs proteins?
Inhibits GTPase on alpha subunit
What type of G-protein does the pertussis toxin affect?
Gi
How does the pertussis toxin affect Gi proteins?
Prevents GTP replacing GDP on the alpha subunit