L8 GPCRs Flashcards
Which is the largest receptor family
GPCRs
Structural features of GPCRs
7 transmembrane spanning domains
Alpha helix 3 in GPCRs
always orientated towards centre of structure
Function of alpha helix 3 in GPCRs
contributes to binding site
What connects TM domains
Intracellular and extracellular loops
N terminus location GPCRs
Points out of the cell - extracellular
C terminus function in GPCRs
regulation of receptor function
What do receptor families share
one or more homologous domains
States of GPCRs
resting and active
Which regions open up the GPCR
TM5 and TM6
TM3 function in GPCR
central location, crucial for transduction of ligand binding
What domains does TM3 send the transduction to
TM5 and TM6
What else can contribute to ligand binding
Extracellular N terminus
PAR receptor
GPCR for thrombin
What activates PAR receptors
proteinases
PAR receptor function
blood clotting and wound healing
Thrombin
protease (enzyme)
Thrombin function
cleaves amino terminus of receptor
Effect of cleaving amino terminus of PAR receptor
activates receptor
What two receptors are involved in blood clotting
thrombin receptor and ADP
Blood thinners interfere with which receptors
thrombin receptor and ADP
Which patients require blood thinners
patients at risk of stroke or clotting
ADP receptor type
purinergic
Allosteric modulator
molecules that act away from ligand binding site
Impact of allosteric modulator
may impact receptor function
Describe the resting GPCR
three inactive components
How is the resting GPCR activated
ligand binding and exchange of GDP for GTP
End result of active GPCR
three separate active components
inactive alpha subunit Gprotein characteristics
alpha subunit has high affinity for GDP
GEF
guanine exchange factor
GEF function
causes GDP to fall off and GTP to come on
RGS
regulators of G protein signalling
How is receptor signalling system adapted
feedback
Olfactory receptors activation
transduced through same trimeric G protein
What do RGS proteins stimulate
GTPase activity
What is duration of signalled by activated trimeric G protein regulated by
rate of GDP hydrolysis by Ga
What do G proteins control production of
second messengers, and ion channels
What are effectors of trimeric G proteins
enzymes
What do G proteins effectors (enzymes) control levels of
second messengers
What is local concentration fo 2nd messengers determined by
rate of production, rate of diffusion and rate of removal
What regulates cAMP production
adenylyl cyclase
What removes cAMP
phosphodiesterase
What does activated adenylyl cyclase catalyse
ATP into cAMP
How many isoforms of adenylate cyclase are there
10
What activates adenylate cyclase
Gas
What inhibits adenylyl cyclase
Gai
What does B2 adreno-receptor regulate
metabolism in liver and skeletal muscle
What does stimulation of cAMP and adenylate cyclase activate
PKA
PKA function in metabolism
sets up signalling cascade that phosphorylates enzymes controlling glycogen metabolism
What is the effect of a stimulus on cell function determined by
receptor and signalling molecules expressed in that cell
