Guillén Jaime, de Almeida Rodrigo F M, Prieto Manuel, Villalaín José
Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Elche-Alicante, Spain.
J Phys Chem B. 2008 Jun 12;112(23):6997-7007. doi: 10.1021/jp7118229. Epub 2008 May 20.
The SARS coronavirus (SARS-CoV) envelope spike (S) glycoprotein, a Class I viral fusion protein, is responsible for the fusion between the membranes of the virus and the target cell. In the present work, we report a study of the binding and interaction with model membranes of a peptide pertaining to the putative fusion domain of SARS-CoV, SARS FP, as well as the structural changes that take place in both the phospholipid and the peptide molecules upon this interaction. From fluorescence and infrared spectroscopies, the peptide ability to induce membrane leakage, aggregation and fusion, as well as its affinity toward specific phospholipids, was assessed. We demonstrate that SARS FP strongly partitions into phospholipid membranes, more specifically with those containing negatively charged phospholipids, increasing the water penetration depth and displaying membrane-activity modulated by the lipid composition of the membrane. Interestingly, peptide organization is different depending if SARS FP is in water or bound to the membrane. These data suggest that SARS FP could be involved in the merging of the viral and target cell membranes by perturbing the membrane outer leaflet phospholipids and specifically interacting with negatively charged phospholipids located in the inner leaflet.
严重急性呼吸综合征冠状病毒（SARS-CoV）包膜刺突（S）糖蛋白是一种I类病毒融合蛋白，负责病毒膜与靶细胞膜之间的融合。在本研究中，我们报告了一项关于与SARS-CoV假定融合域相关的肽SARS FP与模型膜的结合和相互作用的研究，以及这种相互作用发生时磷脂和肽分子中发生的结构变化。通过荧光光谱和红外光谱，评估了该肽诱导膜泄漏、聚集和融合的能力，以及其对特定磷脂的亲和力。我们证明SARS FP强烈分配到磷脂膜中，更具体地说是分配到含有带负电荷磷脂的膜中，增加了水的渗透深度，并显示出受膜脂质组成调节的膜活性。有趣的是，根据SARS FP是在水中还是与膜结合，肽的组织方式是不同的。这些数据表明，SARS FP可能通过扰动膜外小叶磷脂并与位于内小叶的带负电荷磷脂特异性相互作用，参与病毒膜与靶细胞膜的融合。
