Assembly and architecture of endogenous NMDA receptors in adult cerebral cortex and hippocampus
文献类型：期刊论文
| 作者 | Zhang, Ming4,5; Feng, Juan3; Xie, Chun3; Song, Nan3; Jin, Chaozhi2; Wang, Jian2; Zhao, Qun1; Zhang, Lihua1; Wang, Boshuang3,4; Sun, Yidi3 |
| 刊名 | CELL
 |
| 出版日期 | 2025-03-06 |
| 卷号 | 188期号:5页码:24 |
| ISSN号 | 0092-8674 |
| DOI | 10.1016/j.cell.2025.01.004 |
| 英文摘要 | The cerebral cortex and hippocampus are crucial brain regions for learning and memory, which depend on activity-induced synaptic plasticity involving N-methyl-D-aspartate receptors (NMDARs). However, subunit assembly and molecular architecture of endogenous NMDARs (eNMDARs) in the brain remain elusive. Using conformation- and subunit-dependent antibodies, we purified eNMDARs from adult rat cerebral cortex and hippocampus. Three major subtypes of GluN1-N2A-N2B, GluN1-N2B, and GluN1-N2A eNMDARs were resolved by cryoelectron microscopy (cryo-EM) at the resolution up to 4.2 angstrom. The particle ratio of these three subtypes was 9:7:4, indicating that about half of GluN2A and GluN2B subunits are incorporated into the triheterotetramers. Structural analysis revealed the asymmetric architecture of the GluN1-N2A-N2B receptor throughout the extracellular to the transmembrane layers. Moreover, the conformational variations between GluN1-N2B and GluN1-N2A-N2B receptors revealed the distinct biophysical properties across different eNMDAR subtypes. Our findings imply the structural and functional complexity of eNMDARs and shed light on structure-based therapeutic design targeting these eNMDARs in vivo. |
| WOS关键词 | D-ASPARTATE RECEPTOR ; LONG-TERM POTENTIATION ; SYNAPTIC PLASTICITY ; SUBUNIT COMPOSITION ; CRYO-EM ; FUNCTIONAL-PROPERTIES ; SPLICE VARIANTS ; NR2 SUBUNIT ; RAT-BRAIN ; ACTIVATION |
| 资助项目 | STI2030 Major Projects[2022ZD0212700] ; National Natural Science Foundation of China[32221003] ; National Natural Science Foundation of China[22322411] ; CAS Youth Inter-disciplinary Team and the Talent Plan of Shanghai Branch, Chinese Academy of Sciences ; Shanghai Municipal Science and Technology Major Project[184319071000] ; Shanghai Municipal Science and Technology Major Project[19140903102] ; National Natural Science Foundation of China[32371005] ; Research Fund for International Young Scientists[32400787] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:001442077400001 |
| 出版者 | CELL PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/316548]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Li, Yang; Zhu, Shujia |
| 作者单位 | 1.Chinese Acad Sci, Dalian Inst Chem Phys, Natl Chromatog R&A Ctr, CAS Key Lab Separat Sci Analyt Chem,State Key Lab, Dalian 116023, Peoples R China 2.Beijing Inst Life, Natl Ctr Prot Sci Beijing, Beijing Proteome Res Ctr, State Key Lab Med Prote, Beijing 102206, Peoples R China 3.Chinese Acad Sci, Inst Neurosci, CAS Ctr Excellence Brain Sci & Intelligence Techno, Shanghai 200031, Peoples R China 4.Univ Chinese Acad Sci, Beijing, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Neurol & Psychiat Res & Drug Discovery, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Ming,Feng, Juan,Xie, Chun,et al. Assembly and architecture of endogenous NMDA receptors in adult cerebral cortex and hippocampus[J]. CELL,2025,188(5):24. |
| APA | Zhang, Ming.,Feng, Juan.,Xie, Chun.,Song, Nan.,Jin, Chaozhi.,...&Zhu, Shujia.(2025).Assembly and architecture of endogenous NMDA receptors in adult cerebral cortex and hippocampus.CELL,188(5),24. |
| MLA | Zhang, Ming,et al."Assembly and architecture of endogenous NMDA receptors in adult cerebral cortex and hippocampus".CELL 188.5(2025):24. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。