Cryo-EM Structures of Apo, Agonist- and Antagonist-Bound Heteromeric Kainate Receptors

Kainate receptors (KARs) mediate excitatory synaptic transmission and regulate neurotransmitter release. In the central nervous system, KARs predominantly exist as heterotetramers comprising low_affinity (GluK1_3) and high_affinity (GluK4_5) subunits, with GluK2/GluK5 being the most abundant. To elucidate their conformational transitions, we determined the cryo_electron microscopy (cryo_EM) structures of GluK2/GluK5 KARs in the apo and distinct ligand_bound states. The apo structure revealed compact packing with extensive inter_subunit interactions between the ligand_binding domains (LBDs) beyond the conserved D1-D1 upper_lobe contacts. The glutamate_bound structure exhibited enhanced packin