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Structure paper

タイトル	Cryo-EM structures of the triheteromeric NMDA receptor and its allosteric modulation.
ジャーナル・号・ページ	Science, Vol. 355, Issue 6331, Year 2017
掲載日	2017年3月24日
著者	Wei Lü / Juan Du / April Goehring / Eric Gouaux /
PubMed 要旨	-methyl-d-aspartate receptors (NMDARs) are heterotetrameric ion channels assembled as diheteromeric or triheteromeric complexes. Here, we report structures of the triheteromeric GluN1/GluN2A/GluN2B ...-methyl-d-aspartate receptors (NMDARs) are heterotetrameric ion channels assembled as diheteromeric or triheteromeric complexes. Here, we report structures of the triheteromeric GluN1/GluN2A/GluN2B receptor in the absence or presence of the GluN2B-specific allosteric modulator Ro 25-6981 (Ro), determined by cryogenic electron microscopy (cryo-EM). In the absence of Ro, the GluN2A and GluN2B amino-terminal domains (ATDs) adopt "closed" and "open" clefts, respectively. Upon binding Ro, the GluN2B ATD clamshell transitions from an open to a closed conformation. Consistent with a predominance of the GluN2A subunit in ion channel gating, the GluN2A subunit interacts more extensively with GluN1 subunits throughout the receptor, in comparison with the GluN2B subunit. Differences in the conformation of the pseudo-2-fold-related GluN1 subunits further reflect receptor asymmetry. The triheteromeric NMDAR structures provide the first view of the most common NMDA receptor assembly and show how incorporation of two different GluN2 subunits modifies receptor symmetry and subunit interactions, allowing each subunit to uniquely influence receptor structure and function, thus increasing receptor complexity.
リンク	Science / PubMed:28232581 / PubMed Central
手法	EM (単粒子)
解像度	4.5 - 6.0 Å
構造データ	8579 5uow EMDB-8579, PDB-5uow: Triheteromeric NMDA receptor GluN1/GluN2A/GluN2B in complex with glycine, glutamate, MK-801 and a GluN2B-specific Fab, at pH 6.5 手法: EM (単粒子) / 解像度: 4.5 Å EMDB-8580: membrane protein 手法: EM (単粒子) / 解像度: 4.5 Å 8581 5up2 EMDB-8581, PDB-5up2: Triheteromeric NMDA receptor GluN1/GluN2A/GluN2B in complex with glycine, glutamate, Ro 25-6981, MK-801 and a GluN2B-specific Fab, at pH 6.5 手法: EM (単粒子) / 解像度: 6.0 Å EMDB-8583: membrane protein 手法: EM (単粒子) / 解像度: 4.5 Å
化合物	ChemComp-GLU: GLUTAMIC ACID / グルタミン酸 ChemComp-BMK: (5S,10R)-5-methyl-10,11-dihydro-5H-5,10-epiminodibenzo[a,d][7]annulene / MK-801 / 神経伝達物質YM ChemComp-NAG*: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン
由来	xenopus laevis (アフリカツメガエル) mus musculus (ハツカネズミ)
キーワード	MEMBRANE PROTEIN