G Protein Coupled Receptor I Flashcards
Ligand binding to GCPR leads to changes in…
concentration of intracellular mediators
ion permeability at PM
GPCR structure and activators
- extracellular N + intracellular C
- 7 TM helices, 3 extracellular loops, 3 intracellular loops
light, Ca2+, odorants, small molecules, proteins
Classes of GPCRs
Class A = Rhodopsin-like
Class B = Secretin-like
Class C = Glutamate-like
– receptors from different classes share no sequence similarity = molecular convergence
Class A GPCRs
E/DRY motif at cytoplasmic end of 3 TMD
prolines at specific positions
Group 1a = small ligands (buried binding site)
Group 1b = peptides (binding site N, extcell loops, TMD)
Group 1c = glycoprotein hormone (large extcell domain)
Ionic Lock
stabilizes and inactivates B2-adrenergic receptor
between TM3 and TM6
mutations = spontaneous activation
agonist binding = TM3+TM6 apart – G protein binds
Two-State model of Receptor Actiavation
spontaneous receptor activation (resting - active)
agonist promotes isomerization to activated state
antagonist binds to resting and active state
inverse agonist bind to resting
Class B GPCR
peptide agonists interact with extracellular N and TMD
(hot dog in a bun)
activate Gs/adenylyl cyclase
Receptor Activity Modulating Proteins
alters ligand binding selectivity of Class B receptors
- calcitonin receptor + RAMP1/RAMP3 changes binding preference to amylin
Adhesion GPCRs
large N terminal domain (cell-cell adhesion/bind to ECM)
cleave GPCR auto-proteolysis inducing domain = activate
Class C GPCR
small molecule bind to extracellular N (venus flytrap)
activation of RMD of receptor
GABA(B) Receptors
GABA(B1) binds agonist — no signal
GABA(B2) signals to G protein — no bind
- co-express to traffic to PM
Frizzled and Taste 2 Receptors
- respond to WNT proteins (no need G proteins)
- recognize bitter chemicals – poison
—- TR2 polymorphisms = individual aversions
