Receptors Flashcards
What is the structure of GPCR
7 transmembrane helices (integral membrane protein)
GPCR extracellular side
Ligand binding
GPCR intracellular side
G protein binding —> induces conformational chance
Ligand binding signal active
GDP attached to alpha subunit unit; Ligand binds making 1 helice move inducing conformational change releasing GDP and binding GTP.
Ligand binding signal inactive
G alpha connected to GTP dissociated from Gby subunits; then G alpha hydrolyzes GTP to GDP + pi to turn inactive
What GPCR is Epi an agonist for
Beta 2 adrenergic receptor
What does G alpha attached to GTP have high affinity for?
Adenyly Cyclase which will signal to make CAMP to produce fight or flight response
1st messenger
Ligand (ex epi)
2nd messenger
Relay signal from membrane to target protein inside cell (ex CAMP targeting PKA)
Protein Kinase A
2 regulatory subunits, each with 2 camp binding sites (and alanine)
What happens after camp binds to the regulatory sub unit
The catalytic subunit will transfer a phosphate from ATP to a serine or threonine side chain on target proteins
What is the conformational change of PKA caused by camp?
2 camps disconnect catalytic subunits from regulatory subunits that then move on to Phosphorylated
Amplification
Each active enzyme can activate multiple downstream components ; nonlinear pathways; multiple steps allow levels of regulation (glucagon released for low blood glucose)
How is the GPCR pathway turned of
Reversing or blocking events that were turned on; GTP to GDP and Pi to stop AC from making camp
Phosphotases
Remove phosphate groups through hydrolysis; reverse proteins that added phosphate groups to target proteins (kinases)
Phosphodiesterase
Hydorlyze camp so pka regulatory subunits reassociate with catalytic subunits to turn pka off
Arrestin
Binds to GPCR to terminate G protein signaling by binding to GPCR
Stimulatory G protein
AC is continually active leading to increased cellular camp concentrations