BACKGROUND Plasmodium vivax merozoite surface protein 3α (PvMSP3α) is a promising vaccine candidate which has shown strong association with immunogenicity and protectiveness. Its use is however complicated by evolutionary plasticity features which enhance immune evasion. Low complexity regions (LCRs) provide plasticity in surface proteins of Plasmodium species, but its implication in vaccine design remain unexplored. Here population genetic, comparative phylogenetic and structural biology analysis was performed on the gene encoding PvMSP3α. RESULTS Three LCRs were found in PvMSP3α block II. Both the predicted tertiary structure of the protein and the phylogenetic trees based on this region were influenced by the presence of the LCRs. The LCRs were mainly B cell epitopes within or adjacent. In addition a repeat motif mimicking one of the B cell epitopes was found within the PvMSP3a block II low complexity region. This particular B cell epitope also featured rampant alanine substitutions which might impair antibody binding. CONCLUSION The findings indicate that PvMSP3α block II possesses LCRs which might confer a strong phenotypic plasticity. The phenomenon of phenotypic plasticity and implication of LCRs in malaria immunology in general and vaccine candidate genes in particular merits further exploration.

中文翻译：

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PvMSP3α嵌段II中低复杂性区域对蛋白质三级结构的影响及其对免疫逃逸机制的影响。

背景间日疟原虫裂殖子表面蛋白3α（PvMSP3α）是一种很有前途的候选疫苗，已显示出与免疫原性和保护性的强关联。然而，其使用由于增强免疫逃避的进化可塑性特征而变得复杂。低复杂性区域（LCR）可为疟原虫物种的表面蛋白提供可塑性，但其在疫苗设计中的意义尚待探索。在这里，对编码PvMSP3α的基因进行了群体遗传，比较系统发育和结构生物学分析。结果在PvMSP3αII区发现了3个LCR。LCR的存在影响了蛋白质的预测三级结构和基于该区域的系统发育树。LCR主要是在其内部或附近的B细胞表位。另外，在PvMSP3a block II低复杂性区域内发现了模仿B细胞表位之一的重复基序。该特定的B细胞表位还具有猖ramp的丙氨酸取代作用，这可能损害抗体结合。结论研究结果表明，PvMSP3αII具有LCR，可能具有很强的表型可塑性。表型可塑性现象和LCRs在一般的疟疾免疫学以及特别是疫苗候选基因中的意义值得进一步探讨。