8XLL

Structure of the native 2-oxoglutarate dehydrogenase complex (OGDHC) in the adult cortex and hippocampus

Summary for 8XLL

• Entry DOI: 10.2210/pdb8xll/pdb
• EMDB information: 38452
• Descriptor: Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial (1 entity in total)
• Functional Keywords: 2-oxoglutarate dehydrogenase complex (ogdhc), transferase
• Biological source: Rattus norvegicus (Norway rat)
• Total number of polymer chains: 24
• Total formula weight: 574888.46

Authors

Zhang, M.,Feng, J.,Li, Y.,Zhu, S. (deposition date: 2023-12-26, release date: 2025-02-05, Last modification date: 2025-03-19)

Primary citation

Zhang, M.,Feng, J.,Xie, C.,Song, N.,Jin, C.,Wang, J.,Zhao, Q.,Zhang, L.,Wang, B.,Sun, Y.,Guo, F.,Li, Y.,Zhu, S.
Assembly and architecture of endogenous NMDA receptors in adult cerebral cortex and hippocampus.
Cell, 188:1198-1207.e13, 2025

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). 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.

PubMed: 39855198
DOI: 10.1016/j.cell.2025.01.004

Experimental method

ELECTRON MICROSCOPY (3.1 Å)