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Excitatory neurotransmission meditated by glutamate receptors including N-methyl-D-aspartate receptors (NMDARs) is pivotal to brain development and function. NMDARs are heterotetramers composed of GluN1 and GluN2 subunits, which bind glycine and glutamate, respectively, to activate their ion channels. Despite importance in brain physiology, the precise mechanisms by which activation and inhibition occur via subunit-specific binding of agonists and antagonists remain largely unknown. Here, we show the detailed patterns of conformational changes and inter-subunit and -domain reorientation leading to agonist-gating and subunit-dependent competitive inhibition by providing multiple structures in distinct ligand states at 4 Å or better. The structures reveal that activation and competitive inhibition by both GluN1 and GluN2 antagonists occur by controlling the tension of the linker between the ligand-binding domain and the transmembrane ion channel of the GluN2 subunit. Our results provide detailed mechanistic insights into NMDAR pharmacology, activation, and inhibition, which are fundamental to the brain physiology.

The assimilation of atmospheric carbon dioxide (CO2) by microalgae and plants for photosynthesis has not been fully understood. Gaining insight into the intricate structural details of the CO2 scavenging mechanism by the photosynthetic green algae Chlamydomonas reinhardtii can pave the way for utilizing abundant CO2 as a valuable alternative fuel resource. Here, we present a crystal structure of the Chlamydomonas reinhardtii LCI1 channel, which is involved in the CO2-concentrating mechanism (CCM) to assimilate inorganic carbon resources. Combined with X-ray crystallography, mass spectrometry and computational simulation, our data indicate that the LCI1 membrane protein forms a trimeric assembly, in which each protomer conducts uncharged CO2 and shuttles this inorganic carbon species across the cell membrane.