7TE4

Crystal structure of Fab2 anti-GluN2B antibody

7TE4 の概要

• エントリーDOI: 10.2210/pdb7te4/pdb
• 分子名称: Fab2 anti-GluN2B antibody, light chain, Fab anti-GluN2B antibody, heavy chain (3 entities in total)
• 機能のキーワード: fab fragment, immune system
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 94973.62

構造登録者

Tajima, N.,Furukawa, H. (登録日: 2022-01-04, 公開日: 2022-03-02, 最終更新日: 2024-10-30)

主引用文献

Tajima, N.,Simorowski, N.,Yovanno, R.A.,Regan, M.C.,Michalski, K.,Gomez, R.,Lau, A.Y.,Furukawa, H.
Development and characterization of functional antibodies targeting NMDA receptors.
Nat Commun, 13:923-923, 2022

PubMed Abstract: 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.

PubMed: 35177668
DOI: 10.1038/s41467-022-28559-3

実験手法

X-RAY DIFFRACTION (2.456 Å)