3-D STRUCTURE DETERMINATION OF SOLUTE TRANSPORTERS

溶质转运蛋白的 3-D 结构测定

• 批准号: 8362298
• 负责人: Lan Guan
• 金额: $ 0.14万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362298
• 关键词: 3-Dimensional; Cell membrane; Crystallization; Crystallography; Development; Disease; Erythrocytes; Eukaryotic Cell; Exploratory/Developmental Grant; Funding; Glucose; Glucose Transporter; Grant; Human; Insulin; Mutation; National Center for Research Resources; Non-Insulin-Dependent Diabetes Mellitus; Principal Investigator; Radiation; Research; Research Infrastructure; Research Project Grants; Resolution; Resources; Robotics; SLC2A1 gene; Source; Structure; Syndrome; United States National Institutes of Health; cancer cell; cost; glucose disposal; member; overexpression; solute; structural biology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 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。迄今为止，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。