User:Ilya/Yeast/Mating pheromone response pathway/GPCR
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GPCR (G Protein Coupled Receptor)
- 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
- 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
- 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.