PDF(Pubmed)
Abstract：
The membrane surface of enveloped viruses contains dedicated proteins enabling the fusion of the viral with the host cell membrane. Working with these proteins is almost always challenging because they are membrane-embedded and naturally metastable. Fortunately, based on a range of different examples, researchers now have several possibilities to tame membrane fusion proteins, making them amenable for structure determination and immunogen generation. This review describes the structural and functional similarities of the different membrane fusion proteins and ways to exploit these features to stabilise them by targeted mutational approaches. The recent determination of two herpesvirus membrane fusion proteins in prefusion conformation holds the potential to apply similar methods to this group of viral fusogens. In addition to a better understanding of the herpesviral fusion mechanism, the structural insights gained will help to find ways to further stabilise these proteins using the methods described to obtain stable immunogens that will form the basis for the development of the next generation of vaccines and antiviral drugs.
摘要：
包膜病毒的膜表面含有使病毒与宿主细胞膜融合的专用蛋白。使用这些蛋白质几乎总是具有挑战性，因为它们是膜包埋的并且自然亚稳态的。幸运的是,基于一系列不同的例子，研究人员现在有几种可能驯服膜融合蛋白，使它们适合于结构测定和免疫原的产生。这篇综述描述了不同膜融合蛋白的结构和功能相似性，以及利用这些特征通过靶向突变方法稳定它们的方法。最近确定两种融合前构象的疱疹病毒膜融合蛋白具有将类似方法应用于这组病毒融合剂的潜力。除了更好地了解疱疹病毒融合机制，所获得的结构见解将有助于找到使用所描述的方法来进一步稳定这些蛋白质的方法，以获得稳定的免疫原，这将成为开发下一代疫苗和抗病毒药物的基础。
