Topic 3: GCPR Flashcards
what is the structure of hetrotrimeric G protein?
it has 3 portions
- alpha unit
- beta unit
- gamma unit
what is the role of the alpha unit?
- GTPase
- inhibit the gamma and beta units when bonded
what is the role of beta and gamma unit
regulate protein activity
- when the alpha unit is bonded to GTP it loses affinity for the beta and gamma unit which now allows them to be active
what are the steps of GCPR mediated activation of an effector protein?
1) ligand binds activating receptor which activates the alpha unit of G protein
2) the activation of alpha causes conformational change which makes it dissociates from GDP and increases affinity for GTP
3) The GTP binding causes the alpha to lose affinity for both the receptor and the beta and gamma units
4) when the ligand dissociates with the receptor it causes the alpha unit to bind to the effector
5) then the GTP in the alpha unit is hydrolyzed and the alpha unit binds again to the gamma and beta units
what does it mean when GTPase activity is increased?
the job is the GTPase is to hydrolyze GTP which then turns it off, reducing the activity of the effector
what does it mean when GTPase activity is decreased?
the job is the GTPase is to hydrolyze GTP which then turns it off, if the activity is decreased then GTP DOESN’T get hydrolyzed and it increasing the activity of the effector
what are the effector proteins of focus
- adenyl cyclase
- phospholipase C
what does adenylyl cyclase do?
it changes ATP to cAMP by removing 2 phosphates
what is a PKA and what does it do?
cAMP dependant protein kinase A and it mediates most of the effects of cAMP
how can adenylyl cyclase be stimulated?
when a stimulating hormone binds to the receptor and a stimulatory Ga is present
hormone example:
- epinephrine
- glucagon
- ATCH
how can adenylyl cyclase be inhibited?
when a inhibiting hormone binds to the receptor and a inhibitory Ga is present
hormone example:
- adenosine
- PGE1
what are the 2 ways to terminate the signal from the GCPRs that activate the adenylyl cyclase
- change the affinity of the receptor when GTP is bound to the alpha unit
- cAMP phosphodiesterase hydrolyzes any cAMP to 5’-AMP
what is an agonist?
a molecule that mimics the function of the natural hormone
what is an antagonist?
a molecule that occupies to the binding spot of the right molecule to inhibit receptor signalling
what does phospholipase C do?
it cleaves phospholipid PIP2 to generate 2 2nd messenger molecules
- DAG (diacylglycerol)
- inositol 1,4,5-triphophate (IP3)
what does DAG and IP3 do?
IP3- opens channel for calcium to leave ER
DAG- activates protein kinase C
how can signals be amplified?
occurs in various steps in a cascade, each step has an increasing amount in signalling
what is the role of calcium in G protein signalling
it activates many signalling process, in particular it binds to 4 places on calmodulin
what is the role of calmodulin in G protein signalling?
modulates the activity of
- specific transition factors
- protein kinases
- phosphatases
how does a low cytosolic concentration of Ca2+ get maintained?
- by a calcium pump
- Na+ driven calcium exchanger
what’re the types of channels
- voltage gated
- internal ligand gated
- external ligand gated
- mechanically gated
what are the concentrations of Na and K inside and outside the cell
Na+ = 12mM in , 145mM out
K+ = 139mM in, 4mM out
what is a electrochemical gradient and how does it work?
inside is negative -70mV
its the combination of a the concentration gradient with the factors if the electric potential difference
describe the process of visual transduction in the dark
1) 11-cis-rential is bonded to opsin (rhodopsin is inactive)
2) no rhodospin means tranducin is not active so its alpha unit doesn’t dissociate to go activate (PDE) phosphodiesterase so now does not breakdown CGMP
3) High levels of cGMP opens the cGMP gated ion channels
4) open channels allows depolarization
5) the neurotransmitter is released
