Metabotropic glutamate receptors (mGlus) belong to a family of obligate dimeric G protein-coupled receptors (GPCRs), that are activated by the excitatory neurotransmitter, L-glutamate. The binding of glutamate causes the closure of the VFTs and a protomer rearrangement that brings the CRDs and TM domains in close proximity. Dimerization of the mGlus is mandatory for their function, and the rearrangement upon activation of the receptors is a complex allosteric process with the two protomers influencing each other. Allosteric modulators of mGlus bind the TM domain to regulate signaling by themselves or in conjunction with orthosteric ligands. Ultimately, agonists and positive allosteric modulators (PAMs) activate mGlus by stabilizing intermolecular interactions between the protomers which enable G protein coupling to the TM domain. Here you can see a recent cryoEM structure of the human glutamate receptor mGlu5 determined within lipid nanodiscs (PDB code: 8T8M)

#molecularart ... #receptor ... #glutamate ... #membrane ... #nanodisc ... #activation ... #cryoem

Structure rendered with @proteinimaging and depicted with @corelphotopaint