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

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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.
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