5IPU

Cryo-EM structure of GluN1/GluN2B NMDA receptor in the DCKA/D-APV-bound conformation, state 6

Summary for 5IPU

• Entry DOI: 10.2210/pdb5ipu/pdb
• Related: 5IOU 5IOV 5IPQ 5IPR 5IPS 5IPT 5IPV
• EMDB information: 8097 8098 8101 8102 8103 8104 8105 8106
• Descriptor: N-methyl-D-aspartate receptor subunit NR1-8a, Ionotropic glutamate receptor subunit NR2B (2 entities in total)
• Functional Keywords: ligand-gated ion channel, synaptic transmission, signaling protein
• Biological source: Xenopus laevis (African clawed frog); More
• Total number of polymer chains: 4
• Total formula weight: 371771.95

Authors

Zhu, S.,Stein, A.R.,Yoshioka, C.,Lee, C.H.,Goehring, A.,Mchaourab, S.H.,Gouaux, E. (deposition date: 2016-03-09, release date: 2016-04-20, Last modification date: 2024-03-06)

Primary citation

Zhu, S.,Stein, R.A.,Yoshioka, C.,Lee, C.H.,Goehring, A.,Mchaourab, H.S.,Gouaux, E.
Mechanism of NMDA Receptor Inhibition and Activation.
Cell, 165:704-714, 2016

PubMed Abstract: N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated, calcium-permeable ion channels that mediate synaptic transmission and underpin learning and memory. NMDAR dysfunction is directly implicated in diseases ranging from seizure to ischemia. Despite its fundamental importance, little is known about how the NMDAR transitions between inactive and active states and how small molecules inhibit or activate ion channel gating. Here, we report electron cryo-microscopy structures of the GluN1-GluN2B NMDA receptor in an ensemble of competitive antagonist-bound states, an agonist-bound form, and a state bound with agonists and the allosteric inhibitor Ro25-6981. Together with double electron-electron resonance experiments, we show how competitive antagonists rupture the ligand binding domain (LBD) gating "ring," how agonists retain the ring in a dimer-of-dimers configuration, and how allosteric inhibitors, acting within the amino terminal domain, further stabilize the LBD layer. These studies illuminate how the LBD gating ring is fundamental to signal transduction and gating in NMDARs.

PubMed: 27062927
DOI: 10.1016/j.cell.2016.03.028

Experimental method

ELECTRON MICROSCOPY (15.4 Å)