Buzón Víctor, Padrós Esteve, Cladera Josep
Unitat de Biofísica, Departament de Bioquímica i de Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
Biochemistry. 2005 Oct 11;44(40):13354-64. doi: 10.1021/bi050382r.
The interaction of the so-called fusion peptide of the human immunodeficiency virus gp41 envelope glycoprotein with the target cell membrane is believed to trigger the fusion process which allows the entry of the virus into the cell. Many studies on the interaction of the fusion peptide with biological membranes have been carried out using synthetic peptides and model membranes. Due to the variety of experimental systems and sequences used, some controversy exists, concerning mainly the type of structure which triggers membrane destabilization and fusion (alpha helix or beta structure). With the aim of contributing to shed some light on the subject we have undertaken a series of experiments on the interaction of the three most representative fusion sequences with model membranes under the same experimental conditions. The results show that the fusion peptides, which adopt an unordered structure when dissolved in DMSO, form a mixture of aggregated beta and helical + unordered structures in aqueous buffer. Model membranes are shown to enhance the formation of aggregated beta structures. The nature of the membrane binding event, the kinetics of the binding and lipid mixing processes, and the kinetics of the structural changes depend on whether both ends of the fusion sequence or just one bears a positive charge. Analysis of the kinetic data shows that lipid mixing depends on the transformation of unordered + helical structures into aggregated beta structures upon binding to the membrane.
人们认为，人类免疫缺陷病毒gp41包膜糖蛋白的所谓融合肽与靶细胞膜的相互作用会引发融合过程，使病毒能够进入细胞。许多关于融合肽与生物膜相互作用的研究都是使用合成肽和模型膜进行的。由于所使用的实验系统和序列各不相同，目前存在一些争议，主要涉及引发膜不稳定和融合的结构类型（α螺旋或β结构）。为了有助于阐明这一问题，我们在相同的实验条件下，对三种最具代表性的融合序列与模型膜的相互作用进行了一系列实验。结果表明，融合肽在溶解于二甲基亚砜时呈无序结构，而在水性缓冲液中则形成聚集的β结构与螺旋+无序结构的混合物。结果显示，模型膜会促进聚集的β结构的形成。膜结合事件的性质、结合和脂质混合过程的动力学以及结构变化的动力学，取决于融合序列的两端还是只有一端带正电荷。动力学数据分析表明，脂质混合取决于无序+螺旋结构在与膜结合时转变为聚集的β结构。
