User:Ilya/Yeast/Mating pheromone response pathway/GPCR

GPCR (G Protein Coupled Receptor)

Structure
Gαβγ
 * α - Gpa1
 * β - Ste4
 * γ - Ste18


 * membrane recruitment of Ste5 defines a molecular activity for Gβγ
 * seven-spanning membrane proteins: very similar folds but low sequence similarity.
 * 7 transmembrane alpha-helices, 22-24 residues
 * loop between helices 5 & 6 binds Gα

Function

 * Activation:
 * doesn't require GEF activator: a conformational change facilitates release of bound GDP. *Two domains of Galpha pivot and open a cleft leading to release of GDP.
 * G protein * GTP binds and activates/inhibits effector enzyme
 * effector enzyme catalyzes formation of the second messenger
 * Deactivation:
 * GTP quickly hydrolyses to GDP
 * GAP role?


 * In normal Galpha, GAP-like domain is connected to Ras-like domain where GAP binds to Ras*GTP complex during cycling of Ras.


 * There switch domains have been identified, that change position when GTP substitutes for GDP on Galpha. These include residues adjacent to the terminal phosphates of GTP and/or the Mg++ associated with them.
 * The beta subunit of the heterotrimeric G protein has a beta-propeller structure, formed from multiple repeats of a sequence called the WD-repeat.
 * The beta-propeller provides a stable structural support for residues that bind Galpha.


 * G protein + GTP = active state
 * G protein + GDP = inactive state


 * The G Protein is involved in production of Cyclic AMP or cAMP from ATP. This is the major process behind the G Protein. cAMP is actually a second messenger and goes ahead to perform its function.