SIGNAL SEQUENCES--CONFORMATION AND MEMBRANE-BINDING

信号序列——构象和膜结合

• 批准号: 3286947
• 负责人: LILA M GIERASCH
• 金额: $ 8.43万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-01-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3286947
• 关键词: bacterial proteins; biological signal transduction; circular dichroism; conformation; high performance liquid chromatography; infrared spectrometry; lipid bilayer membrane; membrane lipids; membrane proteins; micelles; mitochondria; mutant; nuclear magnetic resonance spectroscopy; peptide structure; protein metabolism; protein sequence; protein signal sequence; secretion; synthetic peptide

Continued studies are proposed to elucidate the mechanisms by which targeting sequences (including signal sequences and organellar localization sequences) facilitate correct localization of nascent polypeptide products. The emphasis of this proposal is the development of sequence/function correlations. We will use chemically synthesized targeting sequences and a number of biophysical methods to analyze them: circular dichroism (CD), nuclear magnetic resonance (NMR), infrared spectroscopy (IR), and surface tensiometry; peptide/lipid interactions will be probed in micelle, vesicle and multilayer systems. Our working hypothesis, supported by our results on signal sequences, is that there are intrinsic properties of targeting sequences that confer upon them the ability to interact productibly with cellular components and to mediate the process of protein localization. These properties will be assessed by biophysical and biochemical study of the isolated targeting sequences, of targeting sequences linked to portions of their cognate protein products, and of targeting sequences in combination with other cellular components (e.g., membranes, SRP, export factors). The importance of the context in which a targeting sequence is presented will also be investigated. Through collaborative interactions, our results will be integrated with genetic and cellular biological characterization of the targeting sequences.

提出了持续的研究以阐明该机制 靶向序列（包括信号序列和细胞器 定位序列）促进新生的正确定位 多肽产品。 该提议的重点是 序列/功能相关性的发展。 我们将使用 化学合成的靶向序列和许多 分析它们的生物物理方法：循环二科运动（CD）， 核磁共振（NMR），红外光谱法（IR）和 表面张力仪；肽/脂质相互作用将在 胶束，囊泡和多层系统。 我们的工作假设， 我们在信号序列上的结果支持的是 赋予它们的靶向序列的内在特性 与细胞成分和互动相互作用的能力和 介导蛋白质定位的过程。 这些属性 将通过生物物理和生化研究评估 孤立的靶向序列，链接到的靶向序列 其同源蛋白产品的一部分和靶向 序列与其他细胞成分结合（例如， 膜，SRP，出口因子）。 上下文在 提出了靶向顺序。 通过协作互动，我们的结果将集成 具有遗传和细胞生物学特征 定位序列。