6CNA

GluN1-GluN2B NMDA receptors with exon 5

Summary for 6CNA

• Entry DOI: 10.2210/pdb6cna/pdb
• EMDB information: 7529
• Descriptor: Glutamate receptor ionotropic, NMDA 1, Glutamate receptor ionotropic, NMDA 2B, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: splicing variant, membrane protein
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 4
• Total formula weight: 375990.61

Authors

Furukawa, H.,Grant, T.,Grigorieff, N. (deposition date: 2018-03-07, release date: 2018-10-03, Last modification date: 2025-05-14)

Primary citation

Regan, M.C.,Grant, T.,McDaniel, M.J.,Karakas, E.,Zhang, J.,Traynelis, S.F.,Grigorieff, N.,Furukawa, H.
Structural Mechanism of Functional Modulation by Gene Splicing in NMDA Receptors.
Neuron, 98:521-529.e3, 2018

PubMed Abstract: Alternative gene splicing gives rise to N-methyl-D-aspartate (NMDA) receptor ion channels with defined functional properties and unique contributions to calcium signaling in a given chemical environment in the mammalian brain. Splice variants possessing the exon-5-encoded motif at the amino-terminal domain (ATD) of the GluN1 subunit are known to display robustly altered deactivation rates and pH sensitivity, but the underlying mechanism for this functional modification is largely unknown. Here, we show through cryoelectron microscopy (cryo-EM) that the presence of the exon 5 motif in GluN1 alters the local architecture of heterotetrameric GluN1-GluN2 NMDA receptors and creates contacts with the ligand-binding domains (LBDs) of the GluN1 and GluN2 subunits, which are absent in NMDA receptors lacking the exon 5 motif. The unique interactions established by the exon 5 motif are essential to the stability of the ATD/LBD and LBD/LBD interfaces that are critically involved in controlling proton sensitivity and deactivation.

PubMed: 29656875
DOI: 10.1016/j.neuron.2018.03.034

Experimental method

ELECTRON MICROSCOPY (4.6 Å)