| Karakas E, Furukawa H: Crystal structure of a heterotetrameric NMDA receptor ion channel. Science 2014, 344:992–997. Lee C-H, Lu W, Michel JC, Goehring A, Du J, Song X, Gouaux E: NMDA receptor structures reveal subunit arrangement and pore architecture. Nature 2014, 511:191–197. |
** First structures of assembled heterotetrameric NMDARs via X-ray crystallographic studies for rat and frog NMDARs, showing alternating subunit arrangement and domain swap between the ATD layer and the LBD layer. |
| 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 2016, 10.1038/nature17679 | ** Cryo-EM structures of three major different agonist-bound classes suggest concerted movements of the ATD and the LBD are required to activate the NMDAR ion channel. The structure-based functional experiments validated the structural observation. |
| Lu W, Du J, Goehring A, Gouaux E: Cryo-EM structures of the triheteromeric NMDA receptor and its allosteric modulation. Science 2017, 355:eaal3729 | ** First structure of the triheteromeric NMDAR using antibody fragments to distinguish highly similar subunits. |
| Regan MC, Grant T, McDaniel MJ, Karakas E, Zhang J, Traynelis SF, Grigorieff N, Furukawa H: Structural Mechanism of Functional Modulation by Gene Splicing in NMDA Receptors. Neuron 2018, 98:521–529 e523. | ** Cryo-EM structure of GluN1b-GluN2B shows the structural organization of the exon 5- encoded motif at the ATD-LBD interface and a channel blocker MK-801 in the TMD. |
| Karakas E, Simorowski N, Furukawa H: Subunit arrangement and phenylethanolamine binding in GluN1/GluN2B NMDA receptors. Nature 2011, 475:249–253. | * Crystal structure of Xenopus GluN1 ATD and rat GluN2B ATD heterodimer shows that the ifenprodil binding site resides at the GluN1- GluN2B subunit interface. This study shows that the pattern of inter-GluN1-GluN2B interactions at ATD is distinct from those of non-NMDARs. |
| Gielen M, Retchless BS, Mony L, Johnson JW, Paoletti P: Mechanism of differential control of NMDA receptor activity by NR2 subunits. Nature 2009, 459:703–707 Yuan H, Hansen KB, Vance KM, Ogden KK, Traynelis SF: Control of NMDA receptor function by the NR2 subunit amino-terminal domain. J Neurosci 2009, 29:1204512058. |
* The subunit identity of ATD and the linker between ATD and LBD (ATD-LBD linker) influences channel open probability of the NMDARs, as shown by swapping the ATD and the ATD-LBD linker between GluN2A, GluN2B and GluN2D subunits. Similarly, authors use GluN2A-GluN2D chimeras to show that the ATD not only influences channel open probability, but also mean open duration and deactivation time courses by extensive patch-clamp experiments. |
| Sobolevsky AI, Rosconi MP, Gouaux E: X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor. Nature 2009, 462:745–756. | * First crystal structure of the intact AMPAR whose overall fold is distinct and less compact compared to the NMDAR. |
| Dolino DM, Chatterjee S, MacLean DM, Flatebo C, Bishop LDC, Shaikh SA, Landes CF, Jayaraman V: The structure- energy landscape of NMDA receptor gating. Nat Chem Biol 2017, 13:1232–1238. | * Single-molecular FRET studies probe different conformational states of the channel gate region of full-length GluN1/GluN2A receptors with several ligands. |
'Declarations of interest: none