GPCR oligomer

Crystallographic structure of the human κ-opioid receptor homo dimer (4djh) imbedded in a cartoon representation of a lipid bilayer. Each protomer is individually rainbow colored (N-terminus = blue, C-terminus = red). The receptor is complexed with the ligand JDTic that is depicted as a space-filling model (carbon = white, oxygen = red, nitrogen = blue).[1]

A GPCR oligomer is a protein complex that consists of a small number (ὀλίγοι oligoi "a few", μέρος méros "part, piece, component") of G protein-coupled receptors (GPCRs). It is held together by covalent bonds or by intermolecular forces. The subunits within this complex are called protomers, while unconnected receptors are called monomers. Receptor homomers consist of identical protomers, while heteromers consist of different protomers.

Receptor homodimers – which consist of two identical GPCRs – are the simplest homomeric GPCR oligomers. Receptor heterodimers – which consist of two different GPCRs – are the simplest heteromeric GPCR oligomers.

The existence of receptor oligomers is a general phenomenon, whose discovery has superseded the prevailing paradigmatic concept of the function of receptors as plain monomers, and has far-reaching implications for the understanding of neurobiological diseases as well as for the development of drugs.[2][3]

  1. ^ PDB: 4DJH​; Wu H, Wacker D, Mileni M, Katritch V, Han GW, Vardy E, Liu W, Thompson AA, Huang XP, Carroll FI, Mascarella SW, Westkaemper RB, Mosier PD, Roth BL, Cherezov V, Stevens RC (March 2012). "Structure of the human κ-opioid receptor in complex with JDTic". Nature. 485 (7398): 327–32. Bibcode:2012Natur.485..327W. doi:10.1038/nature10939. PMC 3356457. PMID 22437504.
  2. ^ Albizu L, Moreno JL, González-Maeso J, Sealfon SC (November 2010). "Heteromerization of G protein-coupled receptors: relevance to neurological disorders and neurotherapeutics". CNS Neurol Disord Drug Targets. 9 (5): 636–50. doi:10.2174/187152710793361586. PMC 3066024. PMID 20632964.
  3. ^ Rozenfeld R, Devi LA (March 2010). "Receptor heteromerization and drug discovery". Trends Pharmacol. Sci. 31 (3): 124–30. doi:10.1016/j.tips.2009.11.008. PMC 2834828. PMID 20060175.