PEPTIDE ANTIBIOTICS

肽类抗生素

• 批准号: 8168567
• 负责人: STEVEN J LUDTKE
• 金额: $ 2.15万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-15 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168567
• 关键词: Cells; Circular Dichroism; Computer Retrieval of Information on Scientific Projects Database; Cryoelectron Microscopy; Cytolysis; Data; Electrons; Funding; Grant; Image; Individual; Institution; Lipids; Membrane; Membrane Lipids; Methods; Modeling; Neutrons; Peptide Antibiotics; Peptides; Phospholipids; Research; Research Personnel; Resources; Roentgen Rays; Source; Specimen; Structure; United States National Institutes of Health; Vesicle; magainin; research study; solid state nuclear magnetic resonance; virtual; Cells; Circular Dichroism; Computer Retrieval of Information on Scientific Projects Database; Cryoelectron Microscopy; Cytolysis; Data; Electrons; Funding; Grant; Image; Individual; Institution; Lipids; Membrane; Membrane Lipids; Methods; Modeling; Neutrons; Peptide Antibiotics; Peptides; Phospholipids; Research; Research Personnel; Resources; Roentgen Rays; Source; Specimen; Structure; United States National Institutes of Health; Vesicle; magainin; research study; solid state nuclear magnetic resonance; virtual

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Magainin is a peptide antibiotic that interacts directly with the lipid membrane in the target cell. The mode of action for magainin and related peptides is formation of large nonselective pores in the membrane leading to cell lysis. A number of methods, like Circular Dichroism, Solid State NMR, Raman Scattering, Neutron Scattering, etc., have been used to infer this mode of action. However, none of those methods has directly visualized the structure of an individual pore, and some puzzling inconsistencies exist in the current models. Here we present a new method for studying peptide/lipid interactions, which employs Cryo-EM to image Magainin-induced pores in phospholipid vesicles. Since the size of the putative pores is quite small for direct observation of individual pores, we are also analyzing the cryo-EM data in a scattering context. That is, performing 'virtual' electron scattering experiments through analysis of the power spectra of selected vesicles. While we hope to directly image individual pores, as a first step this permits observation of the effects of Magainin in bulk specimens, and relating the cryoEM results to previous X-ray and neutron scattering experiments.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 弹药是一种肽抗生素，与靶细胞中的脂质膜直接相互作用。磁蛋白和相关肽的作用方式是在膜上形成大型非选择性孔，导致细胞裂解。许多方法，例如圆形二分性能，固态NMR，拉曼散射，中子散射等，已用于推断这种作用方式。但是，这些方法均未直接看到单个孔的结构，并且当前模型中存在一些令人困惑的不一致之处。在这里，我们提出了一种研究肽/脂质相互作用的新方法，该方法采用冷冻EM在磷脂囊泡中使用杂志诱导的孔进行图像。由于推定的孔的大小非常小，用于直接观察单个孔，因此我们还在散射环境中分析了冷冻EM数据。也就是说，通过分析选定囊泡的功率谱进行“虚拟”电子散射实验。虽然我们希望直接对单个毛孔进行成像，但作为第一步，这允许观察弹药在大型标本中的影响，并将冷冻结果与以前的X射线和中子散射实验相关。