Abstract
Heterodimerization of metabotropic glutamate receptors (mGlus) generates functional units that modulate the synapse activity, and displays strong therapeutic potential for treating brain disorders and psychiatry diseases. Here, Wang et al. solved the cryo-EM structures of mGlu2–mGlu3, and mGlu2–mGlu4 heterodimers in various conformational states, revealing the role of each subunit in the asymmetric signaling of mGlu heterodimers and the molecular basis of their allosteric modulation, and giving a rationale to understand which subunit activates the G protein.