Biosignaling through GPCR Flashcards
GPCR have 7 what in there structure
7 transmembrane helical segments
they are a single polypeptide embedded into the cell membrane that loops 7 times
how does adenylyl cyclase get activated?
once hormone has attached to the GPC receptor, the hormone receptor complex causes GDP to be replaced with GTP and this activates G(s-alpha) protein
G(s-alpha) leaves the complex and goes to activate adenyl cyclase
G proteins are always heterotrimeric?
yes, the ones that are activated by a GPCR
what are the three subunits of the G protein?
alpha, beta, and gamma (y)
what are G protiens
a specialized protein that has the ability to bing to the nucleotide Guanosine triphosphate (GTP) and guanosine diphospahte (GDP)
What subunit of the G protein does GDP/GTP bind to
alpha, once activated alpha- GTP and the beta-gamma dimer dissociate from the GPCR and can flow laterally through the membrane to interact with other receptors/proteins to elicit a response
what does adenylyl cyclase do once activated by G alpha- GTP?
adenyl cyclase is an ENZYME that catalyzes the synthesizes the second messenger cAMP ( using ATP)
what does cAMP do once synthesized with the help of adenyl cyclase?
cAMP now activates PKA ( phosphokinase A) which can go and phosphorylate cells ( this is a response to the hormone)
what is the role of 5’ AMP
to turn off PKA, cAMP gets degraded ( hydrolyzed ) by cyclic nucleotide phosphodiesterase into 5’ AMP (inactive)
explain what GTPase is and what its role is?
it self- inactivates the G- alpha subunit after it was activatd its target. this is done by hydrolyzing GTP. the inactive unit now goes and returns to beta and gamma dimer
what enzyme helps 5’ AMP break down cAMP
cyclic nucleotide phosphodiesterase
describe the structure and role of PKA and why it is essential to have 4 cAMP molecules to activate it?
PKA has a catalytic subunit and a regulatory subunit, the substrate binding cleft cannot be reached unless 4 molecules of cAMP come in to bind to regulatory subunit and free up the cleft. Need 4 because of dimer shape
describe how a tiny amount of ligand can elicit a huge response?
once PKA is activated it goes tp phosphorylate other target cells such as phosphorylase b and glycogen
( glucogen to glucose-1phosphate) to glucose to raise blood glucose levels
name two modulators of GTPase activity ( involved in the signal control )
GTPase activator protien (GAP)
regulators of Gprotien signaling (RGS)
describe desensitization
BARK (b-adrenergic receptor kinase) binds to Gsby and phosphorylates the SER residues. This ups the affinity of the receptor to B- arrestin which when bound to the receptor will cause it to endocyte into the cell. ( decreasing number of receptors on cell membrane )
