G-Protein Coupled Receptors (GPCRs)

The GPCR superfamily is the largest family of membrane proteins and its members are involved in all types of stimulus-response pathways, from intercellular communication to physiological senses and consequently, pathological functions.

Approximately 40 - 50% of currently marketed drugs target GPCRs and so understanding the molecular functionality of these receptors is highly clinically and commercially relevant. Despite the success of GPCR drugs, the reality is that many of them have significant levels of unexplained and undesirable side effects.

Historically, GPCR drugs were assumed to directly activate a GPCR monomer, and trigger the specific receptor response. However, there is now substantial evidence that GPCRs act in groups consisting of pairs of identical receptors (GPCR homodimers), pairs of different receptors (GPCR heterodimers) or larger groups of receptors (GPCR oligomers).

This new knowledge about GPCR dimers and oligomers, coupled with appropriate tools, provide a key to better understanding functionality of existing GPCR drugs, improving their side effect profiles and identifying the next generation of highly specific compounds targeting GPCR complexes.

The arrangements of receptors are shown below.