GPCR Manufacturing and Structural Determination Services

G protein-coupled receptors (GPCRs) comprise the largest druggable protein family in humans. GPCRs are encoded by at least 800 genes accounting for approximately 4% of the human genome. GPCRs are eukaryotic membrane receptors that activate signaling cascades in response to internal and external stimuli such as light and neurotransmitters. As such, GPCRs have vital roles in many physiological processes including, but not limited to, regulating behavior and mood, and controlling the autonomic nervous system. Dysregulated or aberrant GPCR activity has been linked with many human diseases such as Schizophrenia and Alzheimer’s disease. GPCRs are important therapeutic targets for approximately 34% of all FDA approved drugs.

GPCRs are classified into 6 groups -Class A to Class F- according to the sequence homology and functional similarity. Despite the sequence diversity among classes, all GPCRs share conserved structure features. GPCRs are constituted of 7 transmembrane α helices and 6 inter-transmembrane loops. Some GPCRs also contain a large extracellular domain or intracellular domain. The highly dynamic and flexible nature of GPCRs is well-suited for ligand reception and signal transduction across a cell membrane. However, they also make up the principle obstacles to producing active and properly folded recombinant GPCRs for in vitro assay development, 3D structure analysis, and drug discovery programs. Structure Based Design offers GPCR purification services for your research needs.

Additionally, Structure Based Design, Inc is currently working on several GPCR portfolio projects for which we are pursuing hits and are actively seeking investors and collaborators.

SBD Portfolio projects:

  1. Human Dopamin D3 Receptor (DRD3)
  2. 5-hydroxytryptamine receptor 2C (HTR2C)
  3. Sphingosine 1-phosphate receptor 1 (S1PR1)

Figure 1: Crystal structure of DRD3-T4L fusion protein. DRD3 is in magenta and the T4L protein is in cyan.
PDB code: 3PBL

Figure 2: Example of rational GPCR construct design. Asterisk represents thermostability mutations.