title: Structure of the zinc-bound amino-terminal domain of the NMDA receptor NR2B subunit.
abstract: N-methyl-D-aspartate (NMDA) receptors belong to the family of ionotropic glutamate receptors (iGluRs) that mediate the majority of fast excitatory synaptic transmission in the mammalian brain. One of the hallmarks for the function of NMDA receptors is that their ion channel activity is allosterically regulated by binding of modulator compounds to the extracellular amino-terminal domain (ATD) distinct from the L-glutamate-binding domain. The molecular basis for the ATD-mediated allosteric regulation has been enigmatic because of a complete lack of structural information on NMDA receptor ATDs. Here, we report the crystal structures of ATD from the NR2B NMDA receptor subunit in the zinc-free and zinc-bound states. The structures reveal the overall clamshell-like architecture distinct from the non-NMDA receptor ATDs and molecular determinants for the zinc-binding site, ion-binding sites, and the architecture of the putative phenylethanolamine-binding site.
authors.affiliation: WM Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
authors.forename: Erkan
authors.initials: E
authors.lastname: Karakas
authors.forename: Noriko
authors.initials: N
authors.lastname: Simorowski
authors.forename: Hiro
authors.initials: H
authors.lastname: Furukawa
mesh_terms: D000495:Allosteric Site; D000818:Animals; D001921:Brain / Q000196:embryology; D018360:Crystallography, X-Ray / Q000379:methods; D004594:Electrophysiology / Q000379:methods; D005260:Female; D018698:Glutamic Acid / Q000737:chemistry; D008968:Molecular Conformation; D009865:Oocytes / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry*; D014982:Xenopus laevis / Q000378:metabolism; D015032:Zinc / Q000737:chemistry
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D015032:Zinc