EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Development and characterization of functional antibodies targeting NMDA receptors.
ジャーナル・号・ページ	Nat Commun, Vol. 13, Issue 1, Page 923, Year 2022
掲載日	2022年2月17日
著者	Nami Tajima / Noriko Simorowski / Remy A Yovanno / Michael C Regan / Kevin Michalski / Ricardo Gómez / Albert Y Lau / Hiro Furukawa /
PubMed 要旨	N-methyl-D-aspartate receptors (NMDARs) are critically involved in basic brain functions and neurodegeneration as well as tumor invasiveness. Targeting specific subtypes of NMDARs with distinct ...N-methyl-D-aspartate receptors (NMDARs) are critically involved in basic brain functions and neurodegeneration as well as tumor invasiveness. Targeting specific subtypes of NMDARs with distinct activities has been considered an effective therapeutic strategy for neurological disorders and diseases. However, complete elimination of off-target effects of small chemical compounds has been challenging and thus, there is a need to explore alternative strategies for targeting NMDAR subtypes. Here we report identification of a functional antibody that specifically targets the GluN1-GluN2B NMDAR subtype and allosterically down-regulates ion channel activity as assessed by electrophysiology. Through biochemical analysis, x-ray crystallography, single-particle electron cryomicroscopy, and molecular dynamics simulations, we show that this inhibitory antibody recognizes the amino terminal domain of the GluN2B subunit and increases the population of the non-active conformational state. The current study demonstrates that antibodies may serve as specific reagents to regulate NMDAR functions for basic research and therapeutic objectives.
リンク	Nat Commun / PubMed:35177668 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	2.456 - 7.51 Å
構造データ	25843 7te9 EMDB-25843, PDB-7te9: Cryo-EM structure of GluN1b-2B NMDAR complexed to Fab2 class1 手法: EM (単粒子) / 解像度: 3.92 Å 25844 7teb EMDB-25844, PDB-7teb: Cryo-EM structure of GluN1b-2B NMDAR complexed to Fab2 non-active1-like 手法: EM (単粒子) / 解像度: 4.23 Å 25845 7tee EMDB-25845, PDB-7tee: Cryo-EM structure of GluN1b-2B NMDAR complexed to Fab2 Non-active2-like 手法: EM (単粒子) / 解像度: 6.59 Å 25849 7teq EMDB-25849, PDB-7teq: Cryo-EM structure of GluN1b-2B NMDAR in complex with Fab5 active conformation 手法: EM (単粒子) / 解像度: 7.51 Å 25850 7ter EMDB-25850, PDB-7ter: Cryo-EM structure of GluN1b-2B NMDAR in complex with Fab5 non-active2 conformation 手法: EM (単粒子) / 解像度: 5.23 Å 25851 7tes EMDB-25851, PDB-7tes: Cryo-EM structure of GluN1b-2B NMDAR in complex with Fab5 in Non-active1 conformation 手法: EM (単粒子) / 解像度: 4.7 Å 25852 7tet EMDB-25852, PDB-7tet: Cryo-EM structure of GluN1b-2B NMDAR in complex with Fab5 in non-active2-like conformation 手法: EM (単粒子) / 解像度: 4.45 Å PDB-7te4: Crystal structure of Fab2 anti-GluN2B antibody 手法: X-RAY DIFFRACTION / 解像度: 2.456 Å PDB-7te6: Crystal structure of GluN1b-2B ATD complexed to Fab5 anti-GluN2B antibody 手法: X-RAY DIFFRACTION / 解像度: 4.55 Å
化合物	ChemComp-HOH: WATER / 水
由来	rattus norvegicus (ドブネズミ) Mouse (ネズミ) mus musculus (ハツカネズミ) xenopus laevis (アフリカツメガエル)
キーワード	IMMUNE SYSTEM (免疫系) / Fab fragment / SIGNALING PROTEIN/IMMUNE SYSTEM / Fab fragment complexed to the receptor / SIGNALING PROTEIN-IMMUNE SYSTEM complex / Channel / antibody (抗体)