School of Chemistry, Sambalpur University, Jyoti Vihar, Burla, Odisha 768 019, India.
School of Chemistry, Sambalpur University, Jyoti Vihar, Burla, Odisha 768 019, India.
Biochim Biophys Acta Biomembr. 2019 Dec 1;1861(12):183056. doi: 10.1016/j.bbamem.2019.183056. Epub 2019 Aug 29.
The membrane composition modulates membrane fusion by altering membrane physical properties and the structure, organization and dynamics of fusion proteins and peptides. The journey of developing peptide-based viral fusion inhibitors is often stalled by the change in lipid composition of viral and target membranes. This makes it important to study the role of membrane composition on the organization, dynamics and fusion inhibiting abilities of the peptide-based fusion inhibitors. Cholesterol, an important constituent of mammalian cell membrane, modulates bilayer properties in multiple ways and impart its effect on the membrane fusion. We have previously shown that TG-23 peptide derived from phagosomal coat protein, coronin 1, shows significant inhibition of fusion between membranes without cholesterol. In this work, we have studied the effect of the TG-23 peptide on the polyethylene glycol-mediated membrane fusion in presence of different concentrations of membrane cholesterol. Our results show that the inhibitory effect of TG-23 is being completely reversed in cholesterol containing membranes. We have evaluated the structure, organization, dynamics and depth of penetration of TG-23 in membranes having different lipid compositions and its effect on membrane properties. Our results demonstrate that cholesterol does not affect the secondary structure of the peptide, however, alters the depth of penetration of the peptide and modifies peptide organization and dynamics. The cholesterol dependent change in organization and dynamics of the peptide influences its efficacy in membrane fusion. Therefore, we envisage that the study of peptide organization and dynamics is extremely important to determine the effect of peptide on the membrane fusion.
膜成分通过改变膜物理性质以及融合蛋白和肽的结构、组织和动力学来调节膜融合。基于肽的病毒融合抑制剂的研发过程常常因病毒和靶细胞膜中脂质组成的变化而受阻。因此，研究膜成分对基于肽的融合抑制剂的组织、动力学和融合抑制能力的作用非常重要。胆固醇是哺乳动物细胞膜的重要组成部分，它通过多种方式调节双层性质，并对膜融合产生影响。我们之前已经表明，来源于吞噬体衣壳蛋白冠状蛋白 1 的 TG-23 肽在没有胆固醇的情况下显示出对膜融合的显著抑制作用。在这项工作中，我们研究了 TG-23 肽在不同膜胆固醇浓度存在下对聚乙二醇介导的膜融合的影响。我们的结果表明，TG-23 的抑制作用在含胆固醇的膜中完全被逆转。我们评估了具有不同脂质组成的膜中 TG-23 的结构、组织、动力学和穿透深度及其对膜性质的影响。我们的结果表明，胆固醇不会影响肽的二级结构，但会改变肽的穿透深度，并改变肽的组织和动力学。胆固醇依赖性肽的组织和动力学变化会影响其在膜融合中的功效。因此，我们设想肽的组织和动力学研究对于确定肽对膜融合的影响极其重要。
