9IYP

Structure of the human GluN1-N2B NMDA receptors in the Mg2+ bound state

Summary for 9IYP

• Entry DOI: 10.2210/pdb9iyp/pdb
• EMDB information: 61000
• Descriptor: Glutamate receptor ionotropic, NMDA 1, Glutamate receptor ionotropic, NMDA 2B, GLYCINE, ... (6 entities in total)
• Functional Keywords: glun1-n2b nmda receptors, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 365968.65

Authors

Huang, X.,Sun, X.,Zhu, S. (deposition date: 2024-07-31, release date: 2025-03-05, Last modification date: 2025-04-16)

Primary citation

Huang, X.,Sun, X.,Wang, Q.,Zhang, J.,Wen, H.,Chen, W.J.,Zhu, S.
Structural insights into the diverse actions of magnesium on NMDA receptors.
Neuron, 113:1006-, 2025

PubMed Abstract: Magnesium (Mg) is a key regulatory ion of N-methyl-ᴅ-aspartate (NMDA) receptors, including conferring them to function as coincidence detectors for excitatory synaptic transmission. However, the structural basis underlying the Mg action on NMDA receptors remains unclear. Here, we report the cryo-EM structures of GluN1-N2B receptors and identify three distinct Mg-binding pockets. Specifically, site Ⅰ is located at the selectivity filter where an asparagine ring forms coordination bonds with Mg and is responsible for the voltage-dependent block. Sites Ⅱ and Ⅲ are located at the N-terminal domain (NTD) of the GluN2B subunit and involved in the allosteric potentiation and inhibition, respectively. Site Ⅱ consists of three acidic residues, and the combination of three mutations abolishes the GluN2B-specific Mg potentiation, while site Ⅲ overlaps with the Zn pocket, and mutations here significantly reduce the inhibition. Our study enhances the understanding of multifaceted roles of Mg in NMDA receptors and synaptic plasticity.

PubMed: 40010346
DOI: 10.1016/j.neuron.2025.01.021

Experimental method

ELECTRON MICROSCOPY (3.27 Å)