9 - GPCR 1 Flashcards
What defines a GPCR
7 sequence stretches of 25-35 consecutive residues that show a relatively high degree of calculated hydrophobicity
What do each sequence represent
7a helices that span the plasma membrane in a counter-clockwise manner forming a receptor
How many GPCR proteins . are there
> 800
What are some functions of GPCRs
1) Sense extracellular signals
2) Transduce signal intracellularly
3) Act as major drug targets
What are some technological advances that propelled GPCR research
1) Radioligand binding techniques
2) Secondary messenger neurochemistry
3) GPCR protein purification
4) GPCR molecular cloning
5) GPCR crystal structure elucidation
6) Cryo-E structure elucidation
Where is the ligand activation site in most rhodopsin class
Deep in the extracellular mouth
What are the 5 classes of GPCR
G lutamate R hodopsin A dhesion F rizzled/Taste S ecretin
What is the structural determinant of glutamate GPCR
Venus-flytrap domain
What is the structural determinant of adhesion GPCR
Adhesion
GAIN
What is the structural determinant of frizzle/taste GPCR
Cysteine-rich domain
What is the determinant of secretin GPCR
Hormone receptor motif domain
What are the exceptions to the ligand activation site being in the extracellular mouth of most rhodopsin
Large peptide receptors
Protease activated receptors
What occurs to the ligand in protease activated receptors
Ligand is embedded in the N-terminal but only activated by a protease
What does the n-terminus form in the mGluR
Two distinct lobes separated by a cavity
What occurs when glutamate binds
Binds in cavity
Causes lobes to close around the ligand (Venus-flytrap)
What has a similar mechanism to the mGluR family
GABAb
What do adhesion GPCR family have
Large N-terminal
What do some adhesion GPCR bind to
ECM proteins
How do GPCRs activate G-proteins
Conformational switch from inactive to active state
What do GPCRs do
Amplify receptor signal while agonist is resident on receptor
What determines the type of signal from GPCRs
a family
What does Gs stimulate
cAMP formation
What does Gi/o inhibit
cAMP, large BY signal
What does Gq stimulate
Phospholipase-C
Mobilise calcium protein kinase-C
What are some BY subunit signals (5)
1) Modulate adenylyl cyclase
2) Inhibit N-type calcium channels
3) Activate phospholipase C
4) Activate GIRK potassium channels
5) Activate PI3 kinase
What does opening GIRK do
Block action potentials and hyperpolarise the cell membrane
What do Gi interact closely with
GIRK channels
How does coupling with GIRK and VGCC make Gi inhibitory protiens
GIRK - inhibits action potentials
VGCC - inhibits neurotransmitter release
