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	Cryo-EM of autoantibody-bound NMDA receptors reveals antigenic hotspots in an active immunization model of anti-NMDAR encephalitis.
ジャーナル・号・ページ	Sci Adv, Vol. 12, Issue 3, Page eaeb4249, Year 2026
掲載日	2026年1月16日
著者	Junhoe Kim / Farzad Jalali-Yazdi / Brian E Jones / Gary L Westbrook / Eric Gouaux /
PubMed 要旨	Autoantibodies targeting synaptic membrane proteins are associated with autoimmune encephalitis manifested by seizures, psychosis, and memory dysfunction. Anti--methyl-d-aspartate receptor (NMDAR) ...Autoantibodies targeting synaptic membrane proteins are associated with autoimmune encephalitis manifested by seizures, psychosis, and memory dysfunction. Anti--methyl-d-aspartate receptor (NMDAR) encephalitis, a prototype of these autoimmune synaptic disorders, is unexpectedly common. Unfortunately, how the native repertoire of anti-NMDAR autoantibodies recognizes NMDARs and the precise locations of antigenic epitopes remain poorly understood. Here, we used an active immunization model that closely mimics the human disease to immunize adult mice with intact GluN1/GluN2A receptors, resulting in fulminant autoimmune encephalitis. Serum was collected at 6 weeks postimmunization for single-particle cryo-electron microscopy of GluN1/GluN2A receptors complexed with purified polyclonal anti-NMDAR autoantibody fragments. Native autoantibodies recognized two distinct binding sites on the GluN1 amino-terminal domain, which we confirmed using monoclonal antibodies bound to native NMDARs purified from mouse brain. Structural analysis of autoantibody-bound NMDAR complexes identified antigenic hotspots within the GluN1 amino-terminal domain. These hotspots provide potential targets for therapeutic intervention.
リンク	Sci Adv / PubMed:41533802 / PubMed Central
手法	EM (単粒子)
解像度	2.76 - 6.56 Å
構造データ	72076 9pzq EMDB-72076, PDB-9pzq: GluN1/GluN2A in complex with polyclonal autoantibody Fab fragments (class 1), glycine- and glutamate-bound state 手法: EM (単粒子) / 解像度: 4.07 Å 72077 9pzr EMDB-72077, PDB-9pzr: GluN1/GluN2A in complex with polyclonal autoantibody Fab fragments (class 2), glycine- and glutamate-bound state 手法: EM (単粒子) / 解像度: 3.92 Å 72078 9pzs EMDB-72078, PDB-9pzs: Native GluN1/GluN2A/GluN2B in complex with 5F11 and 3D2 Fabs (class 1), glycine and glutamate bound state 手法: EM (単粒子) / 解像度: 4.2 Å EMDB-72079: Native GluN1/GluN2A/GluNx in complex with 5F11 and 3D2 Fabs (class 2), glycine and glutamate-bound state 手法: EM (単粒子) / 解像度: 6.56 Å 72080 9pzt EMDB-72080, PDB-9pzt: Native GluN1/GluN2A in complex with 5F11 and 3D2 Fabs (class 3), glycine and glutamate-bound state 手法: EM (単粒子) / 解像度: 6.14 Å 72081 9pzu EMDB-72081, PDB-9pzu: Native GluN1/GluN2B in complex with 5F11 Fab (class 4), glycine and glutamate-bound state 手法: EM (単粒子) / 解像度: 5.36 Å EMDB-72082: Native GluN1/GluNx in complex with 5F11 Fab (class 5), glycine and glutamate-bound state 手法: EM (単粒子) / 解像度: 5.05 Å 72083 9pzv EMDB-72083, PDB-9pzv: Native GluN1/GluN2A in complex with 5F11 and 3D2 Fabs, local ATD dimer 手法: EM (単粒子) / 解像度: 3.92 Å 72084 9pzw EMDB-72084, PDB-9pzw: GluN1/GluN2A in complex with 3D2 Fab, glycine and glutamate-bound state 手法: EM (単粒子) / 解像度: 3.43 Å 72085 9pzx EMDB-72085, PDB-9pzx: GluN1/GluN2A in complex with 3D2 Fab, local ATD dimer 手法: EM (単粒子) / 解像度: 2.76 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン ChemComp-GLY: GLYCINE / グリシン ChemComp-GLU: GLUTAMIC ACID / グルタミン酸
由来	rattus norvegicus (ドブネズミ) mus musculus (ハツカネズミ)
キーワード	TRANSPORT PROTEIN / ligand-gated ion channel / NMDA / antibody / complex / native