The function of the amino terminal domain in NMDA receptor modulation

Abstract

The authors have modelled dimers of the amino terminal domains of these receptors based on their homology with the extracellular dimer of a metabotropic glutamate receptor. Conserved cysteine residues, which have been highlighted as important in previous work, are shown to form a disulphide bridge, stabilizing a four-helix bundle between subunits. This establishes a hinge in the receptor. The model also highlights a zinc binding site in the binding crevice of the NR2a subunit of the receptor that stabilizes the open state of the amino terminal domain. The similar effect of ifenprodil is thus explained by its stabilization of the open state of the amino terminal domain (ATD). The presence of three histidine residues in the zinc site is used to explain the pH dependence of zinc inhibition.