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）：通常假设膜中的双层具有与仅由脂质制成的囊泡中相同的厚度。许多想法都基于这一观点，包括通过疏水性扫描寻找螺旋、膜之间蛋白质分类的概念以及有关纯脂质的大量文献的基本原理。然而，几乎没有测量结果可以作为实际膜厚度的参考点。同样，也没有什么数据可以告诉我们天然膜的面积比例可以被视为未受干扰的双层。我们的初步研究表明，最初在流体马赛克模型中建立的经典观点可能需要修订：蛋白质而不是脂质决定膜尺寸。结果是蛋白质和脂质之间存在张力，其含义值得探索。该提案的主要主题是利用衍射来测量膜蛋白、磷脂和胆固醇对膜厚度的相互影响，确定这些成分在膜中心占据的面积的值，并使用结合生物化学和生物化学的模型系统。分子动力学模拟来辨别基本的化学原理。