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TitleStructural insights into the diverse actions of magnesium on NMDA receptors.
Journal, issue, pagesNeuron, Vol. 113, Issue 7, Page 1006-11018.e4, Year 2025
Publish dateApr 2, 2025
AuthorsXuejing Huang / Xiaole Sun / Qinrui Wang / Jilin Zhang / Han Wen / Wan-Jin Chen / Shujia Zhu /
PubMed AbstractMagnesium (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 ...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.
External linksNeuron / PubMed:40010346
MethodsEM (single particle)
Resolution3.18 - 3.27 Å
Structure data

61000

9iyp

EMDB-61000, PDB-9iyp:
Structure of the human GluN1-N2B NMDA receptors in the Mg2+ bound state
Method: EM (single particle) / Resolution: 3.27 Å

61001

9iyq

EMDB-61001, PDB-9iyq:
Structure of the human GluN1-N2B NMDA receptors in the Mg2+ free state
Method: EM (single particle) / Resolution: 3.18 Å

Chemicals

ChemComp-GLY:
GLYCINE

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-7RC:
(2R)-4-(3-phosphonopropyl)piperazine-2-carboxylic acid

ChemComp-MG:
Unknown entry

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / GluN1-N2B NMDA receptors

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