GPCRs / 7-TM Receptors

G protein-coupled receptors, or GPCRs, also known as 7-Transmembrane receptors (7-TM receptors), are integral membrane proteins that contain seven membrane-spanning helices. As the name suggests they are coupled to heterotrimeric G proteins on the intracellular side of the membrane. Upon ligand binding, the GPCR undergoes a conformational change which is transmitted to the G protein causing activation. Further signal transduction depends on the type of G protein.


GPCRs or 7-TM receptors are activated by a wide variety of ligands including light, olfactory stimulants, peptides, hormones and neurotransmitters. They are grouped into 6 classes based on sequence homology and functional similarity:

  • Class A (or 1) (Rhodopsin-like)
  • Class B (or 2) (Secretin receptor family)
  • Class C (or 3) (Metabotropic glutamate/pheromone)
  • Class D (or 4) (Fungal mating pheromone receptors)
  • Class E (or 5) (Cyclic AMP receptors)
  • Class F (or 6) (Frizzled/Smoothened)

Physiology and Disease

The human genome encodes roughly 350 GPCRs / 7-TM receptors, of which approximately 150 of these have an unknown function. They comprise the largest family of receptors in the human genome and because of their large number, widespread distribution and important roles in cell physiology and biochemistry, they play an important role in medicine.

Diseases involving mutations of GPCRs / 7-TM receptors are relatively rare, however disorders that involve antibodies directed against GPCRs are more common. Typically disease can be caused by:

  • Non-functional receptors (GHRH and familial growth hormone deficiency)
  • Constitutive activation (Rhodopsin and retinitis pigmentosa)
  • Changes in ligand binding specificity (Thyroid-stimulating hormone receptor and hyperthyroidism of pregnancy)
  • Improper receptor processing (vasopressin receptor and diabetes insipidus)
  • Antibodies directed against the receptors (Thyroid stimulation hormone receptor and Graves disease)
  • Constitutively active or inactive G proteins

GPCRS / 7-TM receptors are the target of around half of all modern medicinal drugs. Their expression on the cell surface makes them readily accessible to hydrophilic drugs and their non-uniform expression provides selectivity in activating or blocking physiological events. Agonists and antagonists of GPCRs / 7-TM receptors are used in the treatment of disease in every organ system.