登録情報 データベース : EMDB / ID : EMD-25851 構造の表示 ダウンロードとリンクタイトル Cryo-EM structure of GluN1b-2B NMDAR in complex with Fab5 in Non-active1 conformation マップデータ 詳細 試料複合体 : GluN1b-2B NMDAR complexed to Fab5タンパク質・ペプチド : Glutamate receptor ionotropic, NMDA 1タンパク質・ペプチド : Glutamate receptor ionotropic, NMDA 2Bタンパク質・ペプチド : Fab5 heavy chainタンパク質・ペプチド : Fab5 light chain 詳細機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / cellular response to curcumin / cellular response to corticosterone stimulus / cellular response to magnesium starvation / regulation of postsynaptic cytosolic calcium ion concentration / sensory organ development / sensitization / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration ... neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / cellular response to curcumin / cellular response to corticosterone stimulus / cellular response to magnesium starvation / regulation of postsynaptic cytosolic calcium ion concentration / sensory organ development / sensitization / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / Assembly and cell surface presentation of NMDA receptors / response to hydrogen sulfide / olfactory learning / regulation of protein kinase A signaling / conditioned taste aversion / dendritic branch / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / response to other organism / positive regulation of inhibitory postsynaptic potential / apical dendrite / propylene metabolic process / response to glycine / regulation of ARF protein signal transduction / fear response / response to methylmercury / voltage-gated monoatomic cation channel activity / positive regulation of cysteine-type endopeptidase activity / cellular response to dsRNA / response to carbohydrate / negative regulation of dendritic spine maintenance / regulation of monoatomic cation transmembrane transport / interleukin-1 receptor binding / cellular response to lipid / response to morphine / NMDA glutamate receptor activity / positive regulation of glutamate secretion / response to growth hormone / Synaptic adhesion-like molecules / NMDA selective glutamate receptor complex / RAF/MAP kinase cascade / glutamate-gated calcium ion channel activity / parallel fiber to Purkinje cell synapse / response to manganese ion / NMDA selective glutamate receptor signaling pathway / calcium ion transmembrane import into cytosol / protein heterotetramerization / glutamate binding / neuromuscular process / positive regulation of reactive oxygen species biosynthetic process / regulation of synapse assembly / action potential / glycine binding / positive regulation of calcium ion transport into cytosol / regulation of dendrite morphogenesis / regulation of axonogenesis / male mating behavior / heterocyclic compound binding / suckling behavior / startle response / behavioral response to pain / response to amine / monoatomic cation transmembrane transport / receptor clustering / monoatomic cation transport / regulation of neuronal synaptic plasticity / associative learning / positive regulation of excitatory postsynaptic potential / social behavior / regulation of MAPK cascade / response to magnesium ion / ligand-gated monoatomic ion channel activity / cellular response to organic cyclic compound / extracellularly glutamate-gated ion channel activity / cellular response to glycine / excitatory synapse / positive regulation of dendritic spine maintenance / neuron development / Unblocking of NMDA receptors, glutamate binding and activation / behavioral fear response / phosphatase binding / regulation of postsynaptic membrane potential / small molecule binding / postsynaptic density, intracellular component / cellular response to manganese ion / calcium ion homeostasis / glutamate receptor binding / D2 dopamine receptor binding / prepulse inhibition / multicellular organismal response to stress / monoatomic cation channel activity / long-term memory / detection of mechanical stimulus involved in sensory perception of pain / regulation of neuron apoptotic process / response to electrical stimulus / synaptic cleft / glutamate-gated receptor activity / presynaptic active zone membrane 類似検索 - 分子機能 Glutamate [NMDA] receptor, epsilon subunit, C-terminal / N-methyl D-aspartate receptor 2B3 C-terminus / : / : / Bacterial extracellular solute-binding proteins, family 3 / Solute-binding protein family 3/N-terminal domain of MltF / Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / : / Ligand-gated ion channel ... Glutamate [NMDA] receptor, epsilon subunit, C-terminal / N-methyl D-aspartate receptor 2B3 C-terminus / : / : / Bacterial extracellular solute-binding proteins, family 3 / Solute-binding protein family 3/N-terminal domain of MltF / Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / : / Ligand-gated ion channel / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site / Ionotropic glutamate receptor / Eukaryotic homologues of bacterial periplasmic substrate binding proteins. / Receptor, ligand binding region / Receptor family ligand binding region / Periplasmic binding protein-like I 類似検索 - ドメイン・相同性 Glutamate receptor ionotropic, NMDA 1 / Glutamate receptor ionotropic, NMDA 2B 類似検索 - 構成要素生物種 Rattus norvegicus (ドブネズミ) / Mouse (ネズミ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 4.7 Å 詳細 データ登録者Tajima N / Furukawa H 資金援助 米国, 2件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Institute of Mental Health (NIH/NIMH) MH085926 米国 National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) NS111745 米国
引用ジャーナル : Nat Commun / 年 : 2022タイトル : Development and characterization of functional antibodies targeting NMDA receptors.著者 : Nami Tajima / Noriko Simorowski / Remy A Yovanno / Michael C Regan / Kevin Michalski / Ricardo Gómez / Albert Y Lau / Hiro Furukawa / 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. 履歴 登録 2022年1月5日 - ヘッダ(付随情報) 公開 2022年3月2日 - マップ公開 2022年3月2日 - 更新 2022年3月2日 - 現状 2022年3月2日 処理サイト : RCSB / 状態 : 公開
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