MOLECULAR FACTORS IN BIOMEMBRANE THICKNESSES

生物膜厚度的分子因素

• 批准号: 7053297
• 负责人: DONALD M. ENGELMAN
• 金额: $ 30.07万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7053297
• 关键词: X ray crystallography; biochemistry; biophysics; cell membrane; cholesterol; gel electrophoresis; gel filtration chromatography; hydropathy; laboratory rat; lipid bilayer membrane; mass spectrometry; membrane proteins; molecular dynamics; phospholipids

DESCRIPTION (provided by applicant): It is often assumed that bilayers in membranes have the thicknesses that they would have in vesicles made from the lipids alone. Many ideas rest on this view, including hydrophobicity scans to find helices, notions of protein sorting between membranes, and the rationale for the huge literature on pure lipids. Yet almost no measurements exist as points of reference for the thicknesses of actual membranes. Similarly, there are few data to inform us of the proportion of the area of a natural membrane that can be regarded as an unperturbed bilayer. Our preliminary studies suggest that the classical view, first established in the Fluid Mosaic Model, may be in need of revision: proteins rather than lipids set membrane dimensions. A consequence is that strain exists between protein and lipid, and the implications will be fascinating to explore. The principal themes of this proposal are to use diffraction to measure the mutual influences of membrane proteins, phospholipid and cholesterol on membrane thickness, to establish values for the areas occupied by these components at the membrane center, and to use model systems that combine biochemistry and molecular dynamics simulations to discern the underlying chemical principles.

描述（由申请人提供）：通常认为膜中的双层具有它们在单独由脂质制成的囊泡中所具有的厚度。许多想法都基于这一观点，包括通过疏水性扫描来寻找螺旋，蛋白质在膜之间分选的概念，以及大量纯脂质文献的基本原理。然而，几乎没有测量存在作为实际膜的厚度的参考点。同样，也没有什么数据能告诉我们，一个天然膜的面积比例，可以被视为一个未扰动的双层。我们的初步研究表明，经典的观点，首先建立在流体镶嵌模型，可能需要修订：蛋白质，而不是脂质设置膜尺寸。结果是蛋白质和脂质之间存在应变，其含义将是迷人的探索。该建议的主要主题是使用衍射来测量膜蛋白、磷脂和胆固醇对膜厚度的相互影响，建立这些组分在膜中心所占据的面积的值，并使用结合了联合收割机生物化学和分子动力学模拟的模型系统来辨别潜在的化学原理。