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Neuron. 2000 Dec;28(3):911-25.

Molecular organization of a zinc binding n-terminal modulatory domain in a NMDA receptor subunit.

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1
Laboratoire de Neurobiologie, CNRS UMR 8544, Ecole Normale Supérieure, 46 Rue d'Ulm, 75005, Paris, France. paoletti@biologie.ens.fr

Abstract

Ionotropic glutamate receptors (iGluRs) bind agonists in a domain that has been crystallized and shown to have a bilobed structure. Eukaryotic iGluRs also possess a second extracellular N-terminal domain related to the bacterial periplasmic binding protein LIVBP. In NMDA receptors, the high-affinity Zn inhibition is eliminated by mutations in the LIVBP-like domain of the NR2A subunit. Using LIVBP structure, we have modeled this domain as two lobes connected by a hinge and show that six residues controlling Zn inhibition form two clusters facing each other across a central cleft. Upon Zn binding the two lobes close tightly around the divalent cation. Thus, the extracellular region of NR2A consists of a tandem of Venus flytrap domains, one binding the agonist and the other a modulatory ligand. Such a functional organization may apply to other eukaryotic iGluRs.

PMID:
11163276
[Indexed for MEDLINE]
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