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).

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 神经递质的跨膜转运对于神经元之间的适当信号传导至关重要。转运过程由不同类型的膜转运蛋白介导，这些膜转运蛋白在控制突触间隙中的神经递质浓度中具有关键作用。总体而言，这些转运蛋白可被分类为细胞内囊泡转运蛋白，其负责将递质从细胞质隔离到突触囊泡中，以及质膜转运蛋白，其负责将释放的递质从细胞外空间隔离。细胞内转运蛋白有三个亚类：囊泡胺转运蛋白（SLC 18）、囊泡抑制性氨基酸转运蛋白家族（SLC 32）和囊泡谷氨酸转运蛋白（SLC 17）。质膜转运蛋白主要有两个亚类：高亲和力谷氨酸转运蛋白和Na+转运蛋白。CL - 耦合传输器。后一个亚类是最大的，包括多巴胺、去甲肾上腺素、甘氨酸和GABA的转运蛋白。 本论文的主要研究目的是通过对囊泡神经递质转运蛋白结构的研究来提高我们对囊泡神经递质转运蛋白的认识。同源建模可以用于为来自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进行特定的功能研究，并可能设计适合特定靶标的小分子（药物设计）。