5B3J

Activation of NMDA receptors and the mechanism of inhibition by ifenprodil

Summary for 5B3J

• Entry DOI: 10.2210/pdb5b3j/pdb
• Descriptor: NMDA glutamate receptor subunit, Glutamate receptor ionotropic, NMDA 2B, Fab, heavy chain, ... (6 entities in total)
• Functional Keywords: nmda receptor, transport protein
• Biological source: Xenopus laevis (African clawed frog); More
• Cellular location: Cell membrane; Multi-pass membrane protein: Q00960
• Total number of polymer chains: 8
• Total formula weight: 263802.81

Authors

Tajima, N.,Karakas, E.,Grant, T.,Simorowski, N.,Diaz-Avalos, R.,Grigorieff, N.,Furukawa, H. (deposition date: 2016-03-01, release date: 2016-05-11, Last modification date: 2024-10-23)

Primary citation

Tajima, N.,Karakas, E.,Grant, T.,Simorowski, N.,Diaz-Avalos, R.,Grigorieff, N.,Furukawa, H.
Activation of NMDA receptors and the mechanism of inhibition by ifenprodil
Nature, 534:63-68, 2016

PubMed Abstract: The physiology of N-methyl-d-aspartate (NMDA) receptors is fundamental to brain development and function. NMDA receptors are ionotropic glutamate receptors that function as heterotetramers composed mainly of GluN1 and GluN2 subunits. Activation of NMDA receptors requires binding of neurotransmitter agonists to a ligand-binding domain (LBD) and structural rearrangement of an amino-terminal domain (ATD). Recent crystal structures of GluN1-GluN2B NMDA receptors bound to agonists and an allosteric inhibitor, ifenprodil, represent the allosterically inhibited state. However, how the ATD and LBD move to activate the NMDA receptor ion channel remains unclear. Here we applied X-ray crystallography, single-particle electron cryomicroscopy and electrophysiology to rat NMDA receptors to show that, in the absence of ifenprodil, the bi-lobed structure of GluN2 ATD adopts an open conformation accompanied by rearrangement of the GluN1-GluN2 ATD heterodimeric interface, altering subunit orientation in the ATD and LBD and forming an active receptor conformation that gates the ion channel.

PubMed: 27135925
DOI: 10.1038/nature17679

Experimental method

X-RAY DIFFRACTION (2.9 Å)