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| Title | Assembly and architecture of endogenous NMDA receptors in adult cerebral cortex and hippocampus. |
|---|---|
| Journal, issue, pages | Cell, Vol. 188, Issue 5, Page 1198-1207.e13, Year 2025 |
| Publish date | Mar 6, 2025 |
Authors | Ming Zhang / Juan Feng / Chun Xie / Nan Song / Chaozhi Jin / Jian Wang / Qun Zhao / Lihua Zhang / Boshuang Wang / Yidi Sun / Fei Guo / Yang Li / Shujia Zhu / ![]() |
| PubMed Abstract | The cerebral cortex and hippocampus are crucial brain regions for learning and memory, which depend on activity-induced synaptic plasticity involving N-methyl-ᴅ-aspartate receptors (NMDARs). ...The cerebral cortex and hippocampus are crucial brain regions for learning and memory, which depend on activity-induced synaptic plasticity involving N-methyl-ᴅ-aspartate receptors (NMDARs). However, subunit assembly and molecular architecture of endogenous NMDARs (eNMDARs) in the brain remain elusive. Using conformation- and subunit-dependent antibodies, we purified eNMDARs from adult rat cerebral cortex and hippocampus. Three major subtypes of GluN1-N2A-N2B, GluN1-N2B, and GluN1-N2A eNMDARs were resolved by cryoelectron microscopy (cryo-EM) at the resolution up to 4.2 Å. The particle ratio of these three subtypes was 9:7:4, indicating that about half of GluN2A and GluN2B subunits are incorporated into the tri-heterotetramers. Structural analysis revealed the asymmetric architecture of the GluN1-N2A-N2B receptor throughout the extracellular to the transmembrane layers. Moreover, the conformational variations between GluN1-N2B and GluN1-N2A-N2B receptors revealed the distinct biophysical properties across different eNMDAR subtypes. Our findings imply the structural and functional complexity of eNMDARs and shed light on structure-based therapeutic design targeting these eNMDARs in vivo. |
External links | Cell / PubMed:39855198 |
| Methods | EM (single particle) |
| Resolution | 3.1 - 9.8 Å |
| Structure data | EMDB-38450, PDB-8xlj: EMDB-38451, PDB-8xlk: EMDB-38452, PDB-8xll: EMDB-61622, PDB-9jnn: ![]() EMDB-61623: Structure of native di-heteromeric GluN1-GluN2A NMDA receptor in rat cortex and hippocampus |
| Chemicals | ![]() ChemComp-NAG: ![]() ChemComp-7RC: |
| Source |
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Keywords | CYTOSOLIC PROTEIN / Native glutamine synthetase / MEMBRANE PROTEIN/IMMUNE SYSTEM / MEMBRANE PROTEIN / native NMDA receptor / adult rat cartex & hippocampus / GluN2A / GluN2B / MEMBRANE PROTEIN-IMMUNE SYSTEM complex / TRANSFERASE / 2-oxoglutarate dehydrogenase complex (OGDHC) |
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