P2Y receptor

[5][6] P2Y receptor proteins display large-scale structural domains typical of GPCRs, consisting of seven hydrophobic transmembrane helices connected by three short extracellular loops and three variably sized intracellular loops; an extracellular N-terminus; and an intracellular C-terminus.

[8] In addition, several polar residues found within the transmembrane helices are highly conserved across both species and receptor subtypes.

[6] Despite this, the individual P2Y subtypes are highly conserved across species, with human and mouse P2Y receptors sharing 95% of amino acids.

[7] Recent x-ray crystallography of the human P2Y12 receptor has shown several structural irregularities in regions that are typically highly conserved across GPCRs.

[10] Oscillation of Ca2+ concentration is directly affected by the signal-transduction activity of P2Y1; specifically, through protein kinase C phosphorylation of Thr339 in the carboxy terminus of the P2Y1 receptor.

[4][16][17] In addition to established uses, pharmaceutical research has been conducted into the role of P2Y receptors in osteoporosis,[2] diabetes,[19] and cardio-protection.

[20][17] The biological effects of P2Y receptor activation depends on how they couple to downstream signalling pathways, either via Gi, Gq/11 or Gs G proteins.

P2Y 12 structure as generated by PYMOL with color-coded helices
Clopidogrel (Plavix), an inhibitor of the P2Y12 receptor, was formerly the second best-selling drug in the world [ 13 ]