Cooperative regulation in Acinetobacter baumannii Betaine-Choline-Carnitine transporters and the role of betaine in membrane vesicle trafficking during infection

鲍曼不动杆菌甜菜碱-胆碱-肉碱转运蛋白的协同调节以及甜菜碱在感染过程中膜囊泡运输中的作用

• 批准号: 397707580
• 负责人: Professorin Dr. Christine Maria Ziegler
• 金额: --
• 依托单位: Institut für Biophysik und physikalische Biochemie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/397707580?language=en
• 关键词: Cooperative; regulation; Acinetobacter; baumannii; Betaine

Our proposal focuses on the concerted molecular regulatory mechanism of the set of six BCCTs found in virulent A. baumannii strains. We postulate that together with mechanosensitive channels they are regulated by changes in the physical state of the membrane, e.g., by curvature, membrane tension or the lipid composition of the membrane, and that this lipid-regulation link them to virulence via specific lipid species. We will investigate the structure and function of these BCC membrane transporters and mechanosensitive channels and their cooperative regulation. Moreover, our aim is to decipher which lipid species regulate transcription and activity of the BCCTs and MS channels. In addition, we will investigate whether this group of membrane proteins can be linked to vesicle transport between inner and outer membrane. In summary, we would like to proof that betaine plays an important and complex role during host infection, which might be lead to new therapeutic approaches. Our group will employ the whole structural biology toolbox of X-ray crystallography, cryo-EM single particle analysis and cryo-EM tomography and single molecule FRET microscopy and HDX spectrometry.

我们的提议着重于在有毒baumannii菌株中发现的六个BCCT的一致分子调节机制。我们假设，与机械敏感的通道一起，它们受膜的物理状态的调节，例如曲率，膜张力或膜的脂质组成，而这种脂质调节将它们通过特定脂质物种与毒力联系起来。我们将研究这些BCC膜转运蛋白和机械敏感通道的结构和功能及其合作调节。此外，我们的目的是破译哪种脂质物种调节BCCT和MS通道的转录和活性。此外，我们将研究该膜蛋白是否可以与内膜和外膜之间的囊泡转运相关。总而言之，我们想证明，贝特因在宿主感染期间起重要而复杂的作用，这可能导致新的治疗方法。我们的小组将采用X射线晶体学，Cryo-EM单粒子分析和冷冻EM层析成像以及单分子FRET显微镜和HDX光谱法的整个结构生物学工具箱。