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-Structure paper
タイトル | Activation of NMDA receptors and the mechanism of inhibition by ifenprodil. |
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ジャーナル・号・ページ | Nature, Vol. 534, Issue 7605, Page 63-68, Year 2016 |
掲載日 | 2016年6月2日 |
著者 | Nami Tajima / Erkan Karakas / Timothy Grant / Noriko Simorowski / Ruben Diaz-Avalos / Nikolaus Grigorieff / Hiro Furukawa / |
PubMed 要旨 | 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 ...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. |
リンク | Nature / PubMed:27135925 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.9 - 6.8 Å |
構造データ | EMDB-3352: Activation of NMDA receptors and the mechanism of inhibition by ifenprodil - Active confirmation EMDB-3353: Activation of NMDA receptors and the mechanism of inhibition by ifenprodil - Non-Active 1 Conformation EMDB-3354: Activation of NMDA receptors and the mechanism of inhibition by ifenprodil - Non-Active 2 confirmation EMDB-3355: Activation of NMDA receptors and the mechanism of inhibition by ifenprodil - Class X EMDB-3356: Activation of NMDA receptors and the mechanism of inhibition by ifenprodil - Class Y PDB-5b3j: |
化合物 | ChemComp-NA: ChemComp-HOH: |
由来 |
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キーワード | TRANSPORT PROTEIN / NMDA receptor / SIGNALING PROTEIN / GLUTAMATE RECEPTOR / GLUN1 / GLUN2B / ION CHANNEL |