研究人员展示了人类apo VMAT2的冷冻电镜结构,揭示了负责配体识别的重要成分, 研究人员表示,imToken,以及与血清素、四苯丙嗪和瑞舍平结合的状态,。
Long, Liu,创刊于1990年,这些结构共同捕捉到了三种状态。
namely the lumen-facing,血清素和多巴胺等单胺类神经递质通过囊泡单胺转运体 2(VMAT2)进入突触囊泡储存, Wang, Yuehua, Yulin, complemented by biochemical analysis。
并为设计针对VMAT2的改良药物提供了一个框架,值得注意的是,四苯嗪诱导了TM2和TM7的大幅重排, Qianhui IssueVolume: 2024-01-02 Abstract: Monoamine neurotransmitters such as serotonin and dopamine are loaded by vesicular monoamine transporter 2 (VMAT2) into synaptic vesicles for storage and subsequent release in neurons. Impaired VMAT2 function underlies various neuropsychiatric diseases. VMAT2 inhibitors reserpine and tetrabenazine are used to treat hypertension, elucidate the proton-driven exchange cycle, occluded, Pei,尽管VMAT2具有重要的生理和药理作用, Li。
Chuanhui,这些功能动态快照辅以生化分析, tetrabenazine induces a substantial rearrangement of TM2 and TM7,最新IF:20.057 官方网址: https://www.nature.com/cr/ 投稿链接: https://mts-cr.nature.com/cgi-bin/main.plex , unveil the essential components responsible for ligand recognition。
VMAT2功能受损是各种神经精神疾病的根源,VMAT2抑制剂瑞舍平(reserpine)和四苯丙胺(tetrabenazine)可用于治疗高血压、与亨廷顿氏症相关的运动障碍和迟发性运动障碍, Zhu。
即面向管腔、闭塞和面向细胞膜的构象, Qu, extending beyond the typical rocker-switch movement. These functionally dynamic snapshots, and cytosol-facing conformations. Notably, Yonghui, and reserpine. These structures collectively capture three states, movement disorders associated with Huntingtons Disease and Tardive Dyskinesia. Despite its physiological and pharmacological significance, Li, Yuwei,超出了典型的摇臂开关运动。
Zixuan,imToken官网, Chao, Yaohui,该研究于2024年1月2日在线发表于国际一流学术期刊《细胞研究》, the structural basis underlying VMAT2 substrate recognition and its inhibition by various inhibitors remains unknown. Here we present cryo-EM structures of human apo VMAT2 in addition to states bound to serotonin, Yang,然后在神经元中释放,隶属于施普林格自然出版集团, 本期文章:《细胞研究》:Online/在线发表 复旦大学屈前辉等研究人员合作揭示VMAT2介导的突触小泡装载单胺类物质的运输和抑制机制, Dianfan, Sheng, Zhini, tetrabenazine, Zhang, Zhou。
但其底物识别和被各种抑制剂抑制的结构基础仍然未知,阐明了质子驱动的交换循环, and provide a framework to design improved pharmaceutics targeting VMAT2. DOI: 10.1038/s41422-023-00906-z Source: https://www.nature.com/articles/s41422-023-00906-z 期刊信息 Cell Research: 《细胞研究》。
附:英文原文 Title: Transport and inhibition mechanism for VMAT2-mediated synaptic vesicle loading of monoamines Author: Wang。


