Structure and function studies of the human voltage-gated proton channel HV1

人类电压门控质子通道HV1的结构和功能研究

• 批准号: 279044618
• 负责人: Professor Dr. Boris Musset
• 金额: --
• 依托单位: KNMS Klinikum Nürnberg Medical School GmbH
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/279044618?language=en
• 关键词: Structure; function; studies; human; voltage

The voltage-gated proton channel Hv1 has many implications in physiology. The by far best understood is the charge compensation during the oxidative burst in phagocytosis. Recent publications found additional physiological importance of Hv1 in metastasized breast, colon and rectal cancer cells, sperm, B-cells, microglia, and Basophiles. These implications turn Hv1 into a promising target, to design drugs against cancer, infertility, stroke and immune malfunction.We will investigate the structure and function of Hv1. Therefore we will use the patch clamp technique combined with molecular dynamics simulations to generate and refine a homology model of hHv1. The computer model will be the basis to enhance rational drug design of Hv1. Furthermore we are able to test the efficiency of new drugs directly on expression systems and native cells.

电压门控质子通道Hv1在生理学中具有许多意义。迄今为止最好理解的是在吞噬作用中氧化爆发期间的电荷补偿。最近的出版物发现Hv1在转移的乳腺癌、结肠癌和直肠癌细胞、精子、B细胞、小胶质细胞和嗜碱性粒细胞中具有额外的生理重要性。这些暗示使Hv1成为一个有希望的靶点，用于设计治疗癌症、不孕症、中风和免疫功能障碍的药物。因此，我们将使用膜片钳技术结合分子动力学模拟，以产生和完善的同源性模型的hHv1。该模型的建立将为进一步合理设计Hv1药物奠定基础。此外，我们还能够直接在表达系统和天然细胞上测试新药的效率。