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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 该建议的目的是通过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的葡萄糖转运蛋白的结晶，该葡萄糖转运蛋白得到了NIH探索/发展研究赠款计划R21的支持。 Glut1是主要促进剂超家族的成员，是这些促进转运蛋白的广泛研究。 GLUT4负责胰岛素调节的葡萄糖处置。已经确定了几种疾病，突变导致GLUT1缺乏综合征和II型糖尿病等突变。 GLUT1已显示在少数癌细胞中过表达。重要的是要获得高分辨率结构，并在原子水平上表征运输机理。到目前为止，没有3-D晶体结构可用于任何葡萄糖促进剂。我们将Glut1直接从人类红细胞膜中分离出来。使用高吞吐机器人方法的初始结晶正在进行中。