9PZQ

GluN1/GluN2A in complex with polyclonal autoantibody Fab fragments (class 1), glycine- and glutamate-bound state

9PZQ の概要

• エントリーDOI: 10.2210/pdb9pzq/pdb
• EMDBエントリー: 72076
• 分子名称: polyclonal antibody Fab fragment, termed FabEnc1, Glutamate receptor ionotropic, NMDA 1, Glutamate receptor ionotropic, NMDA 2A (3 entities in total)
• 機能のキーワード: ligand-gated ion channel, nmda, antibody, complex, transport protein
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 426638.10

構造登録者

Kim, J.,Jalali-Yazdi, F.,Gouaux, E. (登録日: 2025-08-11, 公開日: 2025-12-17, 最終更新日: 2026-02-04)

主引用文献

Kim, J.,Jalali-Yazdi, F.,Jones, B.E.,Westbrook, G.L.,Gouaux, E.
Cryo-EM of autoantibody-bound NMDA receptors reveals antigenic hotspots in an active immunization model of anti-NMDAR encephalitis.
Sci Adv, 12:eaeb4249-eaeb4249, 2026

PubMed Abstract: 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.

PubMed: 41533802
DOI: 10.1126/sciadv.aeb4249

実験手法

ELECTRON MICROSCOPY (4.07 Å)