G protein-coupled receptors (GPCRs) are 7 transmembrane proteins that bind extracellular ligands and activate intracellular G proteins. When a ligand binds to a GPCR, it undergoes a conformational change that causes the bound G protein's alpha subunit to exchange GDP for GTP. The activated G protein alpha subunit then detaches from the beta and gamma subunits to initiate downstream signaling, such as by increasing cyclic AMP production. GPCRs function as molecular switches and their signaling persists as long as the G protein alpha subunit remains GTP-bound. Examples of GPCRs include olfactory, adrenergic, and hormone receptors.

1. G PROTEIN COUPLED RECEPTORS
MANJU K M
MSC PLANT SCIENCE

2. • Guanosine nucleotide binding protein
• Serpentine receptor
• 7 transmembrane protein

3. • Ligand binding causes a change in receptor
conformation that activate a particular
G Protein
• A portion of activated G protein binds to a
target protein there by altering targets activity
• Eg: Olfactory receptors
Norepinephrine receptors
Hormone receptors

4. G-protein-coupled receptors (7-TM receptors)
Structure - Single protein with 7 transmembrane regions
Transmembrane
helix
C -Terminal chain
G-Protein
binding region
Variable
intracellular loop
Extracellular
loops
Intracellular loops
N -Terminal chain
HO2C
NH2
VII VI V IV III II IMembrane

5. Structure of G protein

6. 7 transmembrane helices connected by
alternating cytosolic and extra cellular loop
C terminal: inside the cell
N terminal : extra cellular region
Extra cellular portion has unique messenger
binding site
Cytosolic loop allow receptor to interact with G
protein

7. G protein contain 3different subunits
G Alpha
G Beta
G Gamma
G alpha – largest , binds to GTP or GDP
G beta & G gamma permanently bound together

8. Act like MOLECULAR SWITCHES
ON – when bind to GTP
OFF – when bind to GDP
When G alpha bind to GTP it detaches from beta and
gamma complex

9. • When a messenger bind to GPCR the receptor
change its conformation
• G alpha releases its bound GDP and acquires a
new molecule of GTP
• G alpha detaches from G beta & G gamma
complex
• Either the GTP-G alpha subunit or G beta
gamma can initiate signal transduction

11. Activity of G Protein persists as long as
• GTP is bound to G alpha subunit
• G alpha and g beta –g gamma complex remain
separated
This feature allows the signal transduction
pathway to shutdown when the messenger is
utilized
• RGS –Regulators of G Protein signaling Protein

13. Cyclic AMP production is regulated by G protein

15. CALCIUM ION RELEASING & GPCR

16. • The beta & gamma subunits can also trnsduce
signals
• Eg: muscarinic acetylcholine receptors

17. Nobel prize for chemistry 2012 for
studies of GPCR
ROBERT J. LEFKOWITZ BRIAN K . KOBILKA