6MMU

Triheteromeric NMDA receptor GluN1/GluN2A/GluN2A* in the '2-Knuckle-Asymmetric' conformation, in complex with glycine and glutamate, in the presence of 1 micromolar zinc chloride, and at pH 7.4

Summary for 6MMU

• Entry DOI: 10.2210/pdb6mmu/pdb
• EMDB information: 9147 9148 9149 9150 9151 9152 9153 9154 9155 9156 9157 9158 9159 9160 9161 9162 9163 9164 9165
• Descriptor: Glutamate receptor ionotropic, NMDA 1, Glutamate receptor ionotropic, NMDA 2A, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: ligand-gated ion channel, nmda receptor, ionotropic glutamate receptors, membrane protein, transport protein
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 4
• Total formula weight: 384139.05

Authors

Jalali-Yazdi, F.,Chowdhury, S.,Yoshioka, C.,Gouaux, E. (deposition date: 2018-10-01, release date: 2018-11-28, Last modification date: 2024-11-20)

Primary citation

Jalali-Yazdi, F.,Chowdhury, S.,Yoshioka, C.,Gouaux, E.
Mechanisms for Zinc and Proton Inhibition of the GluN1/GluN2A NMDA Receptor.
Cell, 175:1520-1532.e15, 2018

PubMed Abstract: N-methyl-D-aspartate receptors (NMDARs) play essential roles in memory formation, neuronal plasticity, and brain development, with their dysfunction linked to a range of disorders from ischemia to schizophrenia. Zinc and pH are physiological allosteric modulators of NMDARs, with GluN2A-containing receptors inhibited by nanomolar concentrations of divalent zinc and by excursions to low pH. Despite the widespread importance of zinc and proton modulation of NMDARs, the molecular mechanism by which these ions modulate receptor activity has proven elusive. Here, we use cryoelectron microscopy to elucidate the structure of the GluN1/GluN2A NMDAR in a large ensemble of conformations under a range of physiologically relevant zinc and proton concentrations. We show how zinc binding to the amino terminal domain elicits structural changes that are transduced though the ligand-binding domain and result in constriction of the ion channel gate.

PubMed: 30500536
DOI: 10.1016/j.cell.2018.10.043

Experimental method

ELECTRON MICROSCOPY (5.3 Å)