STRUCTURAL & FUNCTIONAL STUDIES OF HUMAN VESICULAR NEUROTRANSMITTER TRANSPORTERS

结构性

• 批准号: 7955126
• 负责人: AXEL T BRUNGER
• 金额: $ 0.22万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7955126
• 关键词: Affinity; Amines; Amino Acid Transporter; Cell membrane; Computer Retrieval of Information on Scientific Projects Database; Coupled; Cytoplasm; Data; Drug Design; Extracellular Space; Family; Funding; Glutamate Transporter; Glycine; Grant; Homology Modeling; Human; Institution; Mediating; Membrane Transport Proteins; Neurons; Neurotransmitters; Norepinephrine; Proteins; Research; Research Personnel; Resources; Role; Signal Transduction; Source; Structural Models; Synaptic Cleft; Synaptic Vesicles; Transmembrane Transport; Transport Process; United States National Institutes of Health; design; dopamine transporter; gamma-Aminobutyric Acid; improved; member; small molecule; structural biology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The transmembrane transport of neurotransmitters is of fundamental importance for proper signaling between neurons. The transport processes are mediated by distinct classes of membrane transport proteins that have key roles in controlling the neurotransmitter concentration in the synaptic cleft. Overall, these transporters can be classed as intracellular vesicular transporters that are responsible for sequestering transmitters from the cytoplasm into synaptic vesicles, and plasma membrane transporters that are responsible for sequestering released transmitter from the extracellular space. There are three subclasses of intracellular transporters: the vesicular amine transporters (SLC18), the vesicular inhibitory amino acid transporter family (SLC32) and the vesicular glutamate transporters (SLC17). There are two major subclasses of plasma membrane transporter: the high-affinity glutamate transporters and the Na+Cl -coupled transporters. The latter subclass is the largest and includes transporters of dopamine, norepinephrine, glycine and GABA. The main research objective is to improve our understanding of the human vesicular neurotransmitter transporters, by utilizing structural data to perform functional studies. Homology modeling could then be used to produce high-quality structural models for proteins from the same family, allowing us to plan specific functional studies on each member, and possibly enabling the design of small molecules that fit the specific targets (drug design).

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 神经递质的跨膜运输对于神经元之间的正确信号传导至关重要。转运过程由不同类别的膜转运蛋白介导，这些蛋白在控制突触间隙中的神经递质浓度方面发挥着关键作用。总体而言，这些转运蛋白可分为细胞内囊泡转运蛋白和质膜转运蛋白，细胞内囊泡转运蛋白负责将递质从细胞质隔离到突触小泡中，质膜转运蛋白负责隔离从细胞外空间释放的递质。细胞内转运蛋白有三个亚类：囊泡胺转运蛋白（SLC18）、囊泡抑制性氨基酸转运蛋白家族（SLC32）和囊泡谷氨酸转运蛋白（SLC17）。质膜转运蛋白有两个主要亚类：高亲和力谷氨酸转运蛋白和 Na+ Cl 偶联转运蛋白。后一亚类是最大的，包括多巴胺、去甲肾上腺素、甘氨酸和 GABA 的转运蛋白。 主要研究目标是通过利用结构数据进行功能研究，提高我们对人类囊泡神经递质转运蛋白的理解。然后，同源建模可用于为同一家族的蛋白质生成高质量的结构模型，使我们能够计划对每个成员的特定功能研究，并可能设计出适合特定目标的小分子（药物设计）。