Pécheur E I, Sainte-Marie J, Bienven e A, Hoekstra D
Department of Physiological Chemistry, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, Groningen, The Netherlands.
J Membr Biol. 1999 Jan 1;167(1):1-17. doi: 10.1007/s002329900466.
Processes such as endo- or exocytosis, membrane recycling, fertilization and enveloped viruses infection require one or more critical membrane fusion reactions. A key feature in viral and cellular fusion phenomena is the involvement of specific fusion proteins. Among the few well-characterized fusion proteins are viral spike glycoproteins responsible for penetration of enveloped viruses into their host cells, and sperm proteins involved in sperm-egg fusion. In their sequences, these proteins possess a "fusion peptide, " a short segment (up to 20 amino acids) of relatively hydrophobic residues, commonly found in a membrane-anchored polypeptide chain. To simulate protein-mediated fusion, many studies on peptide-induced membrane fusion have been conducted on model membranes such as liposomes and have employed synthetic peptides corresponding to the putative fusion sequences of viral proteins, or de novo synthesized peptides. Here, the application of peptides as a model system to understand the molecular details of membrane fusion will be discussed in detail. Data obtained from these studies will be correlated to biological studies, in particular those that involve viral and sperm-egg systems. Structure-function relationships will be revealed, particularly in the context of protein-induced membrane perturbations and bilayer-to-nonbilayer transition underlying the mechanism of fusion. We will also focus on the involvement of lipid composition of membranes as a potential regulating factor of the topological fusion site in biological systems.
诸如胞吞或胞吐作用、膜循环利用、受精以及包膜病毒感染等过程都需要一个或多个关键的膜融合反应。病毒和细胞融合现象的一个关键特征是特定融合蛋白的参与。在少数已被充分表征的融合蛋白中，有负责包膜病毒侵入宿主细胞的病毒刺突糖蛋白，以及参与精卵融合的精子蛋白。在其序列中，这些蛋白拥有一个“融合肽”，这是一段相对疏水残基的短片段（最多20个氨基酸），通常存在于膜锚定的多肽链中。为了模拟蛋白质介导的融合，许多关于肽诱导膜融合的研究在脂质体等模型膜上进行，并采用了与病毒蛋白假定融合序列相对应的合成肽，或从头合成的肽。在此，将详细讨论肽作为一种模型系统在理解膜融合分子细节方面的应用。从这些研究中获得的数据将与生物学研究相关联，特别是那些涉及病毒和精卵系统的研究。结构 - 功能关系将被揭示，尤其是在蛋白质诱导的膜扰动以及融合机制背后的双层到非双层转变的背景下。我们还将关注膜脂质组成作为生物系统中拓扑融合位点潜在调节因子的作用。
