GPR55 is an orphan 7-transmembrane receptor that is abundant in brain and peripheral tissues and has been associated with diseases such as obesity and cancer, as well as neurodegenerative disorders including Parkinson's disease.
Although L-α-lysophosphatidylinositol, a bioactive lipid, is widely recognised as the endogenous ligand of GPR55, the receptor also shows high sensitivity to cannabinoid receptor ligands and can be modulated by endocannabinoids, phytocannabinoids, and synthetic cannabinoids. In addition, GPR55 is known to form heteromers with the cannabinoid receptors CB1 and CB2, resulting in alterations in signal transduction. Allosteric modulation, crosstalk with other receptors and the lack of GPR55-selective ligands has led to controversial observations and complicated the discovery of the pathophysiological role of GPR55.
The instability and low expression of the receptor have hampered the structural characterisation of GPR55, which is required to better understand its pharmacology.
We have investigated thermostabilising mutations and developed an expression and purification protocol to produce pure protein suitable for structure determination, ligand binding, and activity assays.