GPCRs Structure Flashcards
What are the different types of signal molecule targets?
Receptors
Ion channels
Transporters
Enzymes
What is a receptor?
A drug target
What different type of receptors are there?
Kinase linked Receptors- activated by ligand and then they phosphorylase something inside the cell
Ion channels (ligand gated)
Nuclear/ intracellular receptors
G- protein coupled receptors
Give 4 general properties of GPCRs
Single polypeptide
7 transmembrane domains
N terminus is extracellular
C terminus is intracellular
Where can the ligand bind to in a GPCR?
N terminus or transmembrane domains
Give structure of G protein
3 subunits, a, b and y.
GDP attached to a unit
What happens when ligand binds to GPCR?
GPCR changes shape
GDP on a subunit echanges for GTP
A subunit dissociates from y&b subunits (which stays together)
A subunit goes on to interact with effectors
How is G protein deactivated?
GTPas hydrolysed GTP on a subunit to make it GDP
Affinity between a and by subunits is now much higher so they come back together
What effector is stimulated if the G protein is s type?
The a subunit activates adenylyl cyclase.
This converts ATP to cAMP
CAMP then activates PKA, by removing one subunit
PKA phosphorylates stuff in the cell, including VOCC which becomes more active in some cases.
What effector is stimulated if the G protein is q type?
Phospholipase C (PLC) is activated to convert PIP2 in the cell membrane into DAG and IP3. IP3 acts on IP3r to increase release of Ca into cytoplasm from SER DAG and Ca activate protein kinase C (PKC)
How does the pertussis toxin (PTx) affect GPCRs)
It stops GDP being swapped with GTP so the g protein cannot be activated by dissociating the a and by subunits.
How does the cholera toxin (CTx) affect g proteins?
It modifies the G protein so that the GTP on the a unit cannot be hydrolysed to GTP. This means the a and by subunits cannot come back together so the effector is continually stimulated.
