3-D STRUCTURE DETERMINATION OF SOLUTE TRANSPORTERS

溶质转运蛋白的 3-D 结构测定

• 批准号: 8170299
• 负责人: Lan Guan
• 金额: $ 0.03万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170299
• 关键词: 3-Dimensional; Cell membrane; Computer Retrieval of Information on Scientific Projects Database; Crystallization; Crystallography; Development; Disease; Erythrocytes; Eukaryotic Cell; Exploratory/Developmental Grant; Funding; Glucose; Glucose Transporter; Grant; Human; Institution; Insulin; Mutation; Non-Insulin-Dependent Diabetes Mellitus; Research; Research Personnel; Research Project Grants; Resolution; Resources; Robotics; SLC2A1 gene; Source; Structure; Syndrome; United States National Institutes of Health; cancer cell; glucose disposal; member; overexpression; solute

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 aim of this proposal is to study solute transport mechanisms in bacterial and eukaryotic cells by x-ray crystallography. One of our projects is the crystallization of eukaryotic facilitated glucose transporter, which was supported by NIH Exploratory/Developmental Research Grant Program R21. Glut1, a member of the Major Facilitator Superfamily, is an extensively studied representative of these facilitated transporters. Glut4 is responsible for insulin-regulated glucose disposal. Several diseases have been identified with mutations resulting in malfunction of Gluts, such as GLUT1 deficiency syndrome and type II diabetes. GLUT1 has been shown to overexpress in few cancer cells. It is important to obtain a high-resolution structure, as well as to characterize the transport mechanism at an atomic level. Thus far, there is no 3-D crystal structure available for any glucose facilitator. We directly isolate GLUT1 from human Red Blood Cells membranes. Initial crystallization using a high throughput robotic approach is being carried out.

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。子项目和 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。 该提案的目的是通过 X 射线晶体学研究细菌和真核细胞中的溶质转运机制。我们的项目之一是真核促进葡萄糖转运蛋白的结晶，该项目得到了 NIH 探索/发展研究资助计划 R21 的支持。 Glut1 是主要促进子超家族的成员，是这些促进转运蛋白的广泛研究的代表。 Glut4 负责胰岛素调节的葡萄糖处理。多种疾病已被确定为导致 Gluts 功能障碍的突变，例如 GLUT1 缺乏综合征和 II 型糖尿病。 GLUT1 已被证明在少数癌细胞中过度表达。获得高分辨率结构以及在原子水平上表征传输机制非常重要。到目前为止，还没有任何葡萄糖促进剂可用的 3-D 晶体结构。我们直接从人红细胞膜中分离出 GLUT1。正在使用高通量机器人方法进行初始结晶。