Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1038/ncomms14142 |
Conformational dynamics of the human serotonin transporter during substrate and drug binding | |
Moller, Ingvar R.1,2; Slivacka, Marika1,2; Nielsen, Anne Kathrine2; Rasmussen, Soren G. F.3; Gether, Ulrik3; Loland, Claus J.2; Rand, Kasper D.1 | |
2019-04-11 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2019 |
卷号 | 10 |
文章类型 | Article |
语种 | 英语 |
国家 | Denmark |
英文摘要 | The serotonin transporter (SERT), a member of the neurotransmitter:sodium symporter family, is responsible for termination of serotonergic signaling by re-uptake of serotonin (5-HT) into the presynaptic neuron. Its key role in synaptic transmission makes it a major drug target, e.g. for the treatment of depression, anxiety and post-traumatic stress. Here, we apply hydrogen-deuterium exchange mass spectrometry to probe the conformational dynamics of human SERT in the absence and presence of known substrates and targeted drugs. Our results reveal significant changes in dynamics in regions TM1, EL3, EL4, and TM12 upon binding co-transported ions (Na+/K+) and ligand-mediated changes in TM1, EL3 and EL4 upon binding 5-HT, the drugs S-citalopram, cocaine and ibogaine. Our results provide a comprehensive direct view of the conformational response of SERT upon binding both biologically relevant substrate/ions and ligands of pharmaceutical interest, thus advancing our understanding of the structure-function relationship in SERT. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000464093800018 |
WOS关键词 | X-RAY STRUCTURES ; 2 NA+ SITES ; BACTERIAL HOMOLOG ; NEUROTRANSMITTER ; DOPAMINE ; EXCHANGE ; COCAINE ; IBOGAINE ; ION ; NOREPINEPHRINE |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203173 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Copenhagen, Dept Pharm, Prot Anal Grp, DK-2100 Copenhagen, Denmark; 2.Univ Copenhagen, Dept Neurosci, Lab Membrane Prot Dynam, DK-2200 Copenhagen, Denmark; 3.Univ Copenhagen, Dept Neurosci, DK-2200 Copenhagen, Denmark |
推荐引用方式 GB/T 7714 | Moller, Ingvar R.,Slivacka, Marika,Nielsen, Anne Kathrine,et al. Conformational dynamics of the human serotonin transporter during substrate and drug binding[J]. NATURE COMMUNICATIONS,2019,10. |
APA | Moller, Ingvar R..,Slivacka, Marika.,Nielsen, Anne Kathrine.,Rasmussen, Soren G. F..,Gether, Ulrik.,...&Rand, Kasper D..(2019).Conformational dynamics of the human serotonin transporter during substrate and drug binding.NATURE COMMUNICATIONS,10. |
MLA | Moller, Ingvar R.,et al."Conformational dynamics of the human serotonin transporter during substrate and drug binding".NATURE COMMUNICATIONS 10(2019). |
条目包含的文件 | 条目无相关文件。 |
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。
修改评论