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.