Abstract：
Viral spike proteins mutate frequently, but conserved features within these proteins often have functional importance and can inform development of anti-viral therapies which circumvent the effects of viral sequence mutations. Through analysis of large numbers of viral spike protein sequences from several viral families, we found highly (>99%) conserved patterns within their intracellular domains. The patterns generally consist of one or more basic amino acids (arginine or lysine) adjacent to a cysteine, many of which are known to undergo acylation. These patterns were not enriched in cellular proteins in general. Molecular dynamics simulations show direct electrostatic and hydrophobic interactions between these conserved residues in hemagglutinin (HA) from influenza A and B and the phosphoinositide PIP2. Super-resolution microscopy shows nanoscale colocalization of PIP2 and several of the same viral proteins. We propose the hypothesis that these conserved viral spike protein features can interact with phosphoinositides such as PIP2.
摘要：
病毒刺突蛋白经常突变，但是这些蛋白质中的保守特征通常具有功能重要性，并且可以为规避病毒序列突变影响的抗病毒疗法的开发提供信息。通过分析来自几个病毒家族的大量病毒刺突蛋白序列，我们在它们的胞内结构域中发现了高度保守的模式(>99%)。模式通常由一个或多个与半胱氨酸相邻的碱性氨基酸（精氨酸或赖氨酸）组成，已知其中许多经历酰化。这些模式一般在细胞蛋白中不富集。分子动力学模拟显示来自甲型和乙型流感的血凝素(HA)中的这些保守残基与磷酸肌醇PIP2之间的直接静电和疏水相互作用。超分辨率显微镜显示PIP2和几种相同的病毒蛋白的纳米级共定位。我们提出这些保守的病毒刺突蛋白特征可以与磷酸肌醇如PIP2相互作用的假设。
