SGER: A Potential System for Identifying Ligands for Cell Surface Reception.

SGER：一种用于识别细胞表面接收配体的潜在系统。

• 批准号: 0306897
• 负责人: Eugene Nester
• 金额: $ 10万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0306897&HistoricalAwards=false
• 关键词: SGER; Potential; System; Identifying; Ligands

G protein coupled receptors (GPCRs) play critical roles in animal development, cell growth, immune function, and plant defense. Unfortunately, identifying ligands for these cell surface receptors has proven extraordinarily challenging. This project proposes to develop a novel system for addressing this challenge. The system employs a novel class of DNA-protein hybrid molecules as the foundation of a powerful protein display technology. It is based on the observation that VirD2 protein of the bacterial plant pathogen, Agrobacterium tumefaciens, has the remarkable capacity to covalently couple itself to specific DNA recognition sequences. Hence, VirD2 may constitute a generic and versatile tool for covalently linking proteins of interest to the genes that encode them. Such molecules will then be used to generate libraries of DNA-protein hybrids. The small size and biochemical simplicity of the proposed DNA-protein hybrids are expected to overcome biophysical constraints that severely limit the usefulness of "classical" phage and cell-based display systems for GPCR studies. It is expected that the proposed system will have a substantial impact on elucidating GPCR function and biology. Additionally, graduate and postdoctoral students will be trained.

G蛋白偶联受体（gpcr）在动物发育、细胞生长、免疫功能和植物防御等方面发挥着重要作用。不幸的是，为这些细胞表面受体识别配体已经被证明是非常具有挑战性的。本项目建议开发一种新的系统来应对这一挑战。该系统采用了一种新型的dna -蛋白质杂交分子作为强大的蛋白质显示技术的基础。这是基于观察到细菌植物病原体农杆菌（Agrobacterium tumefaciens）的VirD2蛋白具有将自身与特定DNA识别序列共价偶联的显著能力。因此，VirD2可能是一种通用的多功能工具，用于将感兴趣的蛋白质与编码它们的基因共价连接。然后，这些分子将用于生成dna -蛋白质杂交文库。所提出的dna -蛋白质杂交体的小尺寸和生化简单性有望克服严重限制“经典”噬菌体和基于细胞的GPCR研究显示系统有用性的生物物理限制。预计该系统将对阐明GPCR的功能和生物学特性产生重大影响。此外，还将培养研究生和博士后。