Apicomplexan protozoa are intracellular parasites of medical and economic importance. These parasites contain specialized apical complex organelles, including rhoptries, that participate in the process of host cell invasion. Conserved antigens expressed in the rhoptries are rational vaccine targets, but whether conservation of protein structure is a functional requirement for invasion remains unknown. Novel protein structural modeling enables identification of structurally conserved protein families that are not evident by sequence analysis alone. Here we show by AlphaFold2 structural modeling that the rhoptry-associated protein 1 superfamily of the Piroplasmida hemoparasites Babesia and Theileria (pRAP-1) is structurally conserved, with the core conserved region being composed of a globin-like and a 4-helix bundle subdomain. Search for structurally related members of this protein family in other apicomplexan parasites revealed structural homologues of pRAP-1 in several species of Plasmodium, Toxoplasma gondii and other members of the Sarcocystidae family. Based on these structural findings, pRAP-1 is a conserved apical complex protein, but whether these proteins share functional features in different species remains unknown. Identification of widely conserved elements involved in infection in these parasites will enhance our knowledge of invasion mechanisms, and facilitate the design of methods for controlling diseases that affect humans and animals globally.

顶复门原生动物是具有医学和经济重要性的细胞内寄生虫。这些寄生虫含有专门的顶端复杂细胞器，包括参与宿主细胞入侵过程的棒状体。菱形体中表达的保守抗原是合理的疫苗靶标，但蛋白质结构的保守性是否是入侵的功能要求仍不清楚。新颖的蛋白质结构模型能够识别结构保守的蛋白质家族，而这些蛋白质家族仅通过序列分析是无法明显看出的。在这里，我们通过 AlphaFold2 结构模型表明，梨形体血寄生虫巴贝虫和泰勒虫的棒状体相关蛋白 1 超家族 (pRAP-1) 在结构上是保守的，核心保守区域由珠蛋白样和 4 螺旋束子结构域组成。在其他顶复门寄生虫中搜索该蛋白家族的结构相关成员，发现在疟原虫、弓形虫和肉囊虫科其他成员的几种物种中存在 pRAP-1 的结构同源物。基于这些结构发现，pRAP-1是一种保守的顶端复合蛋白，但这些蛋白在不同物种中是否具有相同的功能特征仍不清楚。鉴定与这些寄生虫感染相关的广泛保守的元件将增强我们对入侵机制的了解，并有助于设计控制影响全球人类和动物的疾病的方法。