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Nat Neurosci. 2001 Sep;4(9):894-901.

Allosteric interaction between the amino terminal domain and the ligand binding domain of NR2A.

Author information

1
Department of Pharmacology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA. fzheng@emory.edu

Abstract

Fast desensitization is an important regulatory mechanism of neuronal NMDA receptor function. Only recombinant NMDA receptors composed of NR1/NR2A exhibit a fast component of desensitization similar to neuronal NMDA receptors. Here we report that the fast desensitization of NR1/NR2A receptors is caused by ambient zinc, and that a positive allosteric interaction occurs between the extracellular zinc-binding site located in the amino terminal domain and the glutamate-binding domain of NR2A. The relaxation of macroscopic currents reflects a shift to a new equilibrium due to increased zinc affinity after binding of glutamate. We also show a similar interaction between the ifenprodil binding site and the glutamate binding site of NR1/NR2B receptors. These data raise the possibility that there is an allosteric interaction between the amino terminal domain and the ligand-binding domain of other glutamate receptors. Our findings may provide insight into how zinc and other extracellular modulators regulate NMDA receptor function.

PMID:
11528420
DOI:
10.1038/nn0901-894
[Indexed for MEDLINE]

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