Membrane properties of the OHC system

OHC 系统的膜特性

• 批准号: 10530793
• 负责人: DHASAKUMAR S NAVARATNAM
• 金额: $ 70.24万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-12 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10530793
• 关键词: Affect; Anions; Area; Behavior; Bicarbonates; Cell membrane; Charge; Chlorides; Cholesterol; Cochlea; Complement; Computer Simulation; Contracts; Crosslinker; Cryoelectron Microscopy; Cyclosporine; Cysteine; Detergents; Electric Capacitance; Environment; Family; Fatty Acids; Free Energy; Goals; Hearing; Height; Immobilization; Lateral; Length; Lipids; Mammals; Measurable; Mediating; Membrane; Membrane Lipids; Membrane Potentials; Membrane Proteins; Methodology; Methods; Micelles; Modeling; Molecular; Molecular Conformation; Molecular Motors; Motor; Movement; Mutation; Outer Hair Cells; Paper; Pathology; Pathway interactions; Physiological; Process; Property; Proteins; Resolution; Salicylic Acids; Sampling; Seminal; Structure; System; Temperature; Time; Vesicle; Work; base; combat; conformational conversion; image processing; loss of function; member; millisecond; molecular dynamics; mutant; nanodisk; preservation; protein structure; rat Pres protein; response; sensor; single molecule; voltage

Project Summary In this proposal we hope to build on our efforts defining the cryoEM structure of prestin, the OHC lateral wall motor responsible for cochlear amplification, in the depolarized and contracted state. In this proposal we seek to define the protein's structure in the expanded state brought about by voltage. We will use complementary methods to determine its structure exploiting recent advances in image processing and using temperature and mutations that affect its violtage sensitivity. In addition, we will also be using modeling using molecular dynamics simulations to understand its structure under voltage control.

项目概要 在本提案中，我们希望在定义 prestin（OHC 侧壁）的冷冻电镜结构的努力基础上再接再厉。 负责耳蜗放大的运动，处于去极化和收缩状态。在本提案中，我们寻求 定义电压引起的膨胀状态下蛋白质的结构。我们将使用互补的 利用图像处理的最新进展并使用温度和温度来确定其结构的方法 影响其电压敏感性的突变。此外，我们还将使用分子动力学建模 模拟以了解其在电压控制下的结构。