Four residues of the extracellular N-terminal domain of the NR2A subunit control high-affinity Zn2+ binding to NMDA receptors.

A. Fayyazuddin (1) , A. Villarroel (2) , A. Le Goff (1) , J. Lerma (2) , J. Neyton (1)

1 NEURO - Laboratoire de Neurobiologie (UMR 8544)
2 Istituto Cajal

NMDA receptors are allosterically inhibited by Zn2+ ions in a voltage-independent manner. The apparent affinity for Zn2+ of the heteromeric NMDA receptors is determined by the subtype of NR2 subunit expressed, with NR2A-containing receptors being the most sensitive (IC50, approximately 20 nM) and NR2C-containing receptors being the least sensitive (IC50, approximately 30 microM). Using chimeras constructed from these two NR2 subtypes, we show that the N-terminal LIVBP-like domain of the NR2A subunit controls the high-affinity Zn2+ inhibition. Mutations at four residues in this domain markedly reduce Zn2+ affinity (by up to >500-fold) without affecting either receptor activation by glutamate and glycine or inhibition by extracellular protons and Ni2+ ions, indicating that these residues most likely participate in high-affinity Zn2+ binding.

Domaines: Neurosciences [q-bio.NC]

A. Fayyazuddin, A. Villarroel, A. Le Goff, J. Lerma, J. Neyton. Four residues of the extracellular N-terminal domain of the NR2A subunit control high-affinity Zn2+ binding to NMDA receptors.. Neuron, 2000, 25 (3), pp.683-94. ⟨hal-00115561⟩