Examples of heteromeric receptors, receptor heteromers and receptors with associated modifying proteins. (a) The glutamate NMDA receptor as an example of a heteromeric ionotropic receptor. The NMDA receptor is a tetrameric complex formed by NR1 and NR2 subunits (only two subunits are shown) that bind glycine and glutamate, respectively8. (b) The GABA_B receptor heteromeric receptor as an example of a heteromeric GPCR. GABA_B1 and GABA_B2 subunits establish coiled-coil interactions between their C termini2. (c) The A_2A-D₂ receptor heteromer. The C terminus of the adenosine A_2A receptor binds to the long third intracellular loop of the dopamine D₂ receptor3; whether this and other receptor heteromers are dimeric or higher order oligomeric species remains to be established. (d) The D₁-NMDA receptor heteromer, as an example of a receptor heteromer with a heteromeric receptor as one of the receptor units; the C termini of the NR1 and NR2 (NR2A) subunits bind to different epitopes of the C terminus of the dopamine D₁ receptor14. (e) The MT₁-GPR50 receptor, formed by the association of the melatonin MT₁ receptor and the orphan 7TM protein GPR50. TM domains are probably involved in the oligomerization, while the long C terminus of GPR50 is mostly involved in the modulation of MT₁ receptor function15. (f) The amylin (AMY) receptor, formed by the oligomerization of the calcitonin (CT) receptor and the single transmembrane protein RAMP; the two proteins bind through their N-terminal domains16. In b–f, two subunits are shown for schematic purposes, without ruling out multimerization.