Renoprotection by understanding functional and structural G-protein-coupled receptor activation (A03)

通过了解功能性和结构性 G 蛋白偶联受体激活来保护肾脏 (A03)

• 批准号: 418365095
• 金额: --
• 依托单位: Institut für Medizinische Physik und Biophysik (IMPB)
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/418365095?language=en
• 关键词: Renoprotection; understanding; functional; structural; protein

Autoantibodies (immunoglobulins - IgGs) induce several renal pathologies by targeting the G-protein-coupled receptors (GPCRs), Angiotensin II type 1 and Endothelin-1 type A. We aim to identify and characterize determinants and signaling pathways that are specific for pathogenic IgG binding and receptor-activation as compared to endogenous peptide receptor-agonists. By a combination of G-protein signaling assays in yeast or mammalian cells with biophysical in vitro assays, protein X-ray crystallography and cryo-electron microscopy, we will elucidate molecular insights into autoimmune GPCR activation, which finally will support a rational design of new specific renoprotective drugs.

自身抗体（免疫球蛋白-IgG）通过靶向G蛋白偶联受体（GPCR）、血管紧张素II 1型和内皮素-1 A型诱导多种肾脏病理。我们的目的是确定和表征的决定因素和信号通路，特异性致病性IgG结合和受体激活相比，内源性肽受体激动剂。通过结合酵母或哺乳动物细胞中的G蛋白信号传导测定与生物物理体外测定、蛋白质X射线晶体学和冷冻电子显微镜，我们将阐明自身免疫GPCR激活的分子见解，这最终将支持新的特异性肾保护药物的合理设计。