Gpcr

GPCR ~ aka 7 tranmembrane receptors/heptahelical receptors/ 7 transmembrane domain receptors/ G Protein Linked Receptors protein family of TM receptors that sense molecules outside cell and activate inside signal transduction pathways and ultimately cellular responses Ligand that bind include: Light sensitive compounds Odours Pheromones Hormones Neurotransmitters

Classification 6 classes based on sequence homology and functional similarity Class A to Class F GRAFS (glutamate, Rhodopsin, Adhesion, Frizzled/Taste2, Secretin)

Physiological roles -

wide variety visual sense; rhodopsin smell: odorant/pheromones behavioral and mood regulation: serotonin, dopa, GABA, glutamate immune system activity and inflammation: histamine receptors autonomic nervous system

Structure -

7 TM helices extracellular parts of receptor can be glycosylated: extracellular loops contain 2 highly conserved cysteine reidues that form disulphide bonds

Mechanism -

activated by ligand conformational change  activation of G protein ( depending on type of G protein)

Ligands - examples - 3 types of ligands: agonist, inverse agonist, neutral antagonist

Conformational change - ligand recognized, receptor shifts conformation and mechanically activates G protein - G protein detaches from receptor - GPCR can then activate other G protein or switch to inactive state - GPCR exist in conformational equilibrium between active and inactive state - Activated G protein are bound to GTP - G protein cycle activated GPCR signaling without G protein Receptor Regulation - 2 forms: homologous and heterologous - homologous- activated GPCR is downregulated - heterologous- activated GPCR causes downregulation of a different GPCR ( via phosphorylation of intracellular receptor domain by Protein kinase)

By CAMP- dependent PK - activated PK A phosphorylate GPCR

by GPCR Kinases - phosphorylate only active GPCR - 2 consequences translocation GPCR embedded in Dephosphorylation will bring back to surface Arrestin-linking Prevent from binding to G protein