GPCR Structure Determination By Crystallography

The past decade has seen remarkable progress in the structural biology of GPCRs, yet obtaining 3-dimensional structures of GPCRs, especially in their physiological relevant activation state, is far from routine. Structural analysis of GPCRs for hormones and neurotransmitters has been hindered by their low natural abundance, their inherent structural flexibility and the instability of these proteins in detergent solutions. Biochemical and biophysical studies provide evidence that the flexible and dynamic character of GPCRs is in part responsible for the failure to generate diffraction quality crystals. The Kobilka Lab used two approaches to overcome this structural flexibility and obtained crystal structures of the human β2 adrenergic receptor (β2AR), a receptor for adrenaline and noradrenaline that plays important roles in cardiovascular and pulmonary physiology. The successful crystallization of the β2AR paved the way for obtaining structures of other GPCRs, which has led to the explosion of reports of GPCR structures obtained using similar technology.

For GPCR crystallography, Confometrx has developed its own patented fusion protein technology (US patent no: 8,470,561. See press release here ) and obtained exclusive licensing rights to the T4L patented technology from Stanford University (US patent No. 7790850). We have sub-licensed it to several pharma companies on a per target basis.

For more information, please contact us.