Development and characterization of functional antibodies targeting NMDA receptors.
Development and characterization of functional antibodies targeting NMDA receptors.
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DOI：
10.1038/s41467-022-28559-3
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发表时间：
2022-02-17
影响因子：
16.6
通讯作者：
Furukawa H
中科院分区：
文献类型：
--
作者：
Tajima N;Simorowski N;Yovanno RA;Regan MC;Michalski K;Gómez R;Lau AY;Furukawa H
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. Selective targeting individual subtypes of N-methyl-D-aspartate receptors (NMDARs) is a desirable therapeutic strategy for neurological disorders. Here, the authors report identification of a functional antibody that specifically targets and allosterically down-regulates ion channel activity of the GluN1—GluN2B NMDAR subtype.
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影响因子：
5.3
作者：
Farina, Anthony N.;Blain, Katherine Y.;Nakagawa, Terunaga
通讯作者：
Nakagawa, Terunaga
DOI：
10.1073/pnas.0812952106
发表时间：
2009-03-03
影响因子：
11.1
作者：
Gao, Junjun;Sidhu, Sachdev S.;Wells, James A.
通讯作者：
Wells, James A.
影响因子：
16.2
作者：
Inanobe, A;Furukawa, H;Gouaux, E
通讯作者：
Gouaux, E
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
5.5
作者：
Botello-Smith, Wesley M.;Luo, Yun
通讯作者：
Luo, Yun