L10 G-protein receptor families Flashcards
G protein-coupled receptors: location
membrane
7 transmembrane domains
G protein-coupled receptors: Effector
Enzyme or channel
G protein-coupled receptors: respond to
Hormones or slow NT
G protein-coupled receptors: TimeSOA
Fast
seconds
G protein-coupled receptors: Examples
Adrenoceptors and muscarinic acetylcholine receptors
Salbutamol is an agonist to what and does what
Salbutamol, a b2-adrenoceptor agonist relieves bronchospasm in asthma
acetylcholine agonist to what to activate what
muscarinic acetylcholine receptors activate phospholipase C
adrenaline agonist to what to activate what
ß-adrenoceptors activate adenylate cyclase;
Structure of GPCR
- metabotropic receptors
- 7 transmembrane domain receptors heptahelical receptors
- heterotrimeric G protein
- Gas – activates adenylate cyclase (e.g., b2-adrenoceptor)
- Gai – inhibits adenylate cyclase (e.g., a2 adrenoceptor)
- Gaq – activates phospholipase C (e.g., muscarinic receptor)
b2-Adrenoceptor structure
- extracellular N-terminus
- 7 transmembrane a-helices
- 3 extracellular & 3 intracellular loops
- intracellular C-terminal tail
Protein phosphatases:
dephosphorylate proteins cause inactivation
Protein kinases:
phosphorylate proteins cause activation
The a-subunit binds what and has GTPase activity
GTP and has GTPase activity
3 main classes of Ga protein
- Gas activates adenylate cyclase
- Gai inhibits adenylate cyclase
- Gaq activates phospholipase C
G proteins link GPCRs to effector proteins that generate intracellular second messengers - what msg are generated
- (Gas) adenylate cyclase generates cAMP
- (Gaq) phospholipase C generates inositol 1,4,5-trisphosphate & diacylglycerol
Adenylate cyclase signal transduction pathway
- Agonist activation → conformational change
- Affinity of receptor for G protein increases
Activation of G protein
- Receptor binds to heterotrimeric G protein
- Binding → conformational change in Ga
- GTP binds to Ga
- Ga catalyses exchange of GDP for GTP
Activation of adenylate cyclase enzyme
- Ga dissociates from G(bg)
- Ga binds to adenylate cyclase
- Adenylate cyclase → cyclisation of ATP to cAMP
Inactivation of G protein
- GTP hydrolysed to GDP
- Ga dissociates from adenylate cyclase
- Ga binds to Gbg
Receptor return to resting state
- Receptor dissociates from G protein
- G protein inactivated
- Agonist no longer binds to receptor
- Receptor returns to resting state
ß2-Adrenoceptor signalling cascade
Adrenaline → ß2-adrenoceptor → G(as) → adenylate cyclase → cAMP → cAMP-dependant protein kinase A →relaxation
Muscarinic acetylcholine receptor signalling cascade
acetylcholine → muscarinic acetylcholine receptor →G protein (Gaq)→ phospholipase C →IP3 or DAG→ Ca2+ or PKC →contraction
