Background: Binding appropriate cellular receptors is a crucial step of a lifecycle for any virus. Structure of receptor-binding domain for a viral surface protein has to be determined before the start of future drug design projects. Objectives: Investigation of pH-induced changes in the secondary structure for a capsid peptide with loss of function mutation can shed some light on the mechanism of entrance. Methods: Spectroscopic methods were accompanied by electrophoresis, ultrafiltration, and computational biochemistry. Results: In this study, we showed that a peptide from the receptor-binding domain of Parvovirus B19 VP1 capsid (residues 13-31) is beta-structural at pH=7.4 in 0.01 M phosphate buffer, but alpha- helical at pH=5.0, according to the circular dichroism (CD) spectroscopy results. Results of infra- red (IR) spectroscopy showed that the same peptide exists in both alpha-helical and beta-structural conformations in partial dehydration conditions both at pH=7.4 and pH=5.0. In contrast, the peptide with Y20W mutation, which is known to block the internalization of the virus, forms mostly alpha-helical conformation in partial dehydration conditions at pH=7.4. According to our hypothesis, an intermolecular antiparallel beta structure formed by the wild-type peptide in its tetramers at pH=7.4 is the prototype of the similar intermolecular antiparallel beta structure formed by the corresponding part of Parvovirus B19 receptor-binding domain with its cellular receptor (AXL). Conclusion: Loss of function Y20W substitution in VP1 capsid protein prevents the shift into the beta-structural state by the way of alpha helix stabilization and the decrease of its ability to turn into the disordered state.

中文翻译：

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细小病毒 B19 衣壳受体结合域的结构转变：肽研究

背景：结合适当的细胞受体是任何病毒生命周期的关键步骤。在未来的药物设计项目开始之前，必须确定病毒表面蛋白的受体结合域的结构。目的：研究 pH 诱导的功能丧失突变衣壳肽二级结构的变化可以为了解其进入机制提供一些线索。方法：光谱方法辅以电泳、超滤和计算生物化学。结果：在这项研究中，我们发现来自细小病毒 B19 VP1 衣壳受体结合域的肽（残基 13-31）在 0.01 M 磷酸盐缓冲液中 pH=7.4 时呈 β 结构，但在 pH=5.0 时呈 α 螺旋，根据圆二色性（CD）光谱结果。红外 (IR) 光谱结果表明，在 pH=7.4 和 pH=5.0 的部分脱水条件下，相同的肽以 α 螺旋和 β 结构构象存在。相比之下，具有 Y20W 突变的肽（已知可以阻止病毒的内化）在 pH=7.4 的部分脱水条件下主要形成 α 螺旋构象。根据我们的假设，野生型肽四聚体在pH=7.4时形成的分子间反平行β结构是细小病毒B19受体结合结构域相应部分与其细胞受体形成的类似分子间反平行β结构的原型（AXL）。结论：VP1衣壳蛋白中Y20W取代功能的丧失阻止了通过α螺旋稳定化的方式转变为β结构状态并降低其转变为无序状态的能力。