Lipid plasticity and its relevance for critical biological processes involving membrane reorganization

脂质可塑性及其与涉及膜重组的关键生物过程的相关性

• 批准号: 312634-2006
• 负责人: Lague, Patrick
• 金额: $ 1.46万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2006
• 资助国家: 加拿大
• 起止时间: 2006-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=336294
• 关键词: Lipid; plasticity; its; relevance; critical

The cell membrane is of singular importance for life since it acts as a barrier to the cell environment and controls what goes in and what goes out. Moreover, membrane reorganization by fusion and fission is central to a number of biological processes, such as fertilization, viral infection, vesicle trafficking and cell division. Cell membranes are mainly composed of lipids, forming the framework of the membranes, and proteins, responsible for the biological activities, such as enzymatic processes. The phospholipids constitute the most important class of lipids found in Nature. These molecules are amphipatic, i.e. they have a hydrophilic part, commonly called the polar head, and a hydrophobic part composed of two aliphatic chains. When phospholipids are mixed with water in adequate concentrations, hydrophobic forces cause the aliphatic chains regroup together with the polar heads facing the water. Biological membranes are predominantly arranged as bilayers. Also, proteins with a hydrophobic nature bind to membranes. Recent work from our group shown that a peptide embedded in a bilayer has the ability to change the conformation or "shape" of the lipids. Based on this peptide-induced effect on the lipids, we then proposed the concept of "dynamically induced shape". This concept recognizes that the bilayer membrane is a conformationally plastic and dynamical environment that reacts in a complex way to the presence of impurities or a physical stress. The main objective of the proposed research program is to investigate membrane plasticity for two cases of high biological relevance, membrane fusion from viral infection and membrane fission by antimicrobial peptides. Complementary tools from structural bioinformatics will be used to achieve the goals of this innovative research program.

细胞膜对生命具有特别重要的作用，因为它是细胞环境的屏障，控制着什么进出。此外，通过融合和分裂进行的膜重组是许多生物过程的核心，如受精、病毒感染、囊泡运输和细胞分裂。细胞膜主要由构成膜骨架的脂类和负责生物活性的蛋白质组成，如酶过程。磷脂是自然界中发现的最重要的一类脂类。这些分子是两亲性的，即它们有一个亲水部分，通常被称为极头，以及一个由两个脂肪链组成的疏水部分。当磷脂与适当浓度的水混合时，疏水性作用力导致脂肪链重新聚集在一起，极头面向水。生物膜主要以双层形式排列。此外，具有疏水性的蛋白质与膜结合。我们小组最近的工作表明，嵌入在双层中的多肽具有改变脂类的构象或“形状”的能力。基于这种多肽对血脂的诱导作用，我们提出了“动态诱导形状”的概念。这一概念认识到双层膜是一个构象可塑性的动态环境，它以一种复杂的方式对杂质或物理应力的存在做出反应。该研究计划的主要目标是研究两个具有高度生物学相关性的病例的膜可塑性，这两个病例是病毒感染引起的膜融合和抗菌肽引起的膜分裂。将使用结构生物信息学的补充工具来实现这一创新研究计划的目标。