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