Cryo-EM structures of the triheteromeric NMDA receptor and its allosteric modulation

Added complexity in an asymmetric receptor N -methyl- d -aspartate receptors (NMDARs) are heterotetrameric ion channels that initiate chemical and electrical signals in postsynaptic cells. They play key roles in brain development and function and are the targets of drugs for treating neurological disorders such as schizophrenia, depression, and epilepsy. For the channel to open, it must bind glutamate and glycine and release a blocking magnesium ion. Most NMDARs have three different subunits that bind glycine and glutamine, but structural studies have focused on tetramers of only two subunits. Lü et al. determined the structure of triheteromeric NMDAR. The structural studies show how having three different subunits modifies receptor symmetry and subunit interactions and increases the complexity of receptor regulation. Science , this issue p. eaal3729