BIOL1025 - Hydrophilic signalling - G-protein linked receptor Flashcards
orphan receptor
unknown
G-protein receptor
superfamily of around 800 protein in human genome
structure of G-protein
has 7 pass structure - start N-terminus out of cell and end C terminus
roles
senses
neurotransmission
hormone secretion
chemotaxis etc
trimetric G-protein - large protein
a, b, y
a
has GTP and GDP binding and GTPase activity - GTP to GDP
GTP bind active signalling forming complex GDP - inactive
larges G protein
link to inner membrane associated with receptor
signal transduction by G-protein (inactive state)
GPCR bound to G-protein - if GTP -outer subunit then signal stops
ligand binds at extracellular of GPCR causing conformational change in receptor transmitted to Ga subunit to release GDP exchanging for GTP
which dissociates from Gby dimer and receptor - both active complex
when active
Ga and Gby causes signalling effects
no. of Ga
20
depends on form = different signalling events
Gas, Gai, Gaq
no. Gb
5
some can interact with ion channels
no. Gy
13
when active there are differences in … due to specificity to signals
expression pattern
receptor binding
effects produced in cells
target of activated Gas-subunit
activate GPCR by noradrenaline bind to receptor activates adenylyl cyclase
converting ATP to cAMP activating PkA by binding of cAMP to regulatory subunit of PkA by release catalytic subunit
PkA
protein kinase A - phosphorylating function
GPCR
G-protein coupled receptor
cAMP
cyclic AMP
formation of cAMP from ATP
by adenylyl cyclase - removing 2 phosphate groups = cyclic reaction between O and C3 and C5r = cAMP
cAMP phosphodiesterase function
break down = inactive monophosphate (5’ AMP)
example of Gas-subunit
beta adrenergic receptor
for signalling for neurotransmitter adrenaline
B adrenergic receptor activated PkA
fast or slow
fast activated PkA
phosphorylate and activate other enzymes
slow activated PkA
bind to DNA regulating enzyme and transcription
some prostaglandin receptors
a of activated GP inactivates adenylyl cyclase
receptor binds to GP
Gai binds to adenylyl cyclase and deactivates it decreasing in cAMP
PkA inactivates
Gaq subunit
activated Gaq released - move around and activate phospholipase C
targets PIP2 cleaves = IP3 + DAG
example of Gaq
Antidiuretic hormone
PIP2
phosphatidylinositol-4,5-bisphosphate
PC
phospholipase C
PkC
Protein kinase C
acetylcholine can activate 2 signalling pathways activating PC
IP3
Ca2+
IP3
inositol 1,4,5 triphosphate
binds to Ca2+ in ER
increasing cytoplasmic [Ca2+] from 0.1 to 10 um
IP3 - activating PkC
activates no. protein targets including transcription
terminated by conversion to inactive metabolite
Ca2+ pathway
intracellular messenger
no. cellular process produced by Ca2+ increases and binds to calmodulin = conformational changes - bind protein
act as a switch
termination of Ca2+
by ER pump - pumps Ca2+ back into ER
example of calmodulin
CaM - kinase - calmodulin dependent kinase