NMDA receptor structures reveal subunit arrangement and pore architecture

Article

关键词: AMINO-TERMINAL DOMAIN;    SIZE-EXCLUSION CHROMATOGRAPHY;    LIGAND-BINDING DOMAIN;    HIGH-LEVEL EXPRESSION;    D-ASPARTATE RECEPTORS;    GLUTAMATE-RECEPTOR;    CRYSTAL-STRUCTURE;    ALLOSTERIC INHIBITION;    MOLECULAR-BASIS;    CENTRAL NEURONS;   

DOI  :  10.1038/nature13548

来源: SCIE

【 摘 要 】

N-methyl-D-aspartate (NMDA) receptors are Hebbian-like coincidence detectors, requiring binding of glycine and glutamate in combination with the relief of voltage-dependent magnesium block to open an ion conductive pore across the membrane bilayer. Despite the importance of the NMDA receptor in the development and function of the brain, a molecular structure of an intact receptor has remained elusive. Here we present X-ray crystal structures of the Xenopus laevis GluN1-GluN2B NMDA receptor with the allosteric inhibitor, Ro25-6981, partial agonists and the ion channel blocker, MK-801. Receptor subunits are arranged in a 1-2-1-2 fashion, demonstrating extensive interactions between the amino-terminal and ligand-binding domains. The transmembrane domains harbour a closed-blocked ion channel, a pyramidal central vestibule lined by residues implicated in binding ion channel blockers and magnesium, and a twofold symmetric arrangement of ion channel pore loops. These structures provide new insights into the architecture, allosteric coupling and ion channel function of NMDA receptors.

【 授权许可】

Free