Emerging structural insights into the function of ionotropic glutamate receptors

•Structures of the AMPAR and kainate receptor in multiple states are now available.•These structures show how non-NMDAR iGluRs move to mediate defined functions.•Structures of GluN1/GluN2B show NMDARs and non-NMDARs have distinct architectures.•Despite efforts, a bona fide ‘open channel’ structure remains to be observed.

Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate excitatory neurotransmission crucial for brain development and function, including learning and memory formation. Recently a wealth of structural studies on iGluRs including AMPA receptors (AMPARs), kainate receptors, and NMDA receptors (NMDARs) became available. These studies showed structures of non-NMDARs including AMPAR and kainate receptor in various functional states, thereby providing the first visual sense of how non-NMDAR iGluRs may function in the context of homotetramers. Furthermore, they provided the first view of heterotetrameric NMDAR ion channels, and this illuminated the similarities with and differences from non-NMDARs, thus raising a mechanistic distinction between the two groups of iGluRs. We review mechanistic insights into iGluR functions gained through structural studies of multiple groups.