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刚地弓形虫细胞骨架的定量蛋白质组学分析及高抗原性蛋白质的生物信息学鉴定

Quantitative proteomic analysis of the Toxoplasma gondii cytoskeleton and bioinformatic identification of highly antigenic proteins.

作者信息

Araujo-Ruiz Karina, López-Flores Daniel Ignacio, Martínez-Muné María Karla, García-Sánchez Brenda Yomara, Ramírez-Flores Carlos J, Sandoval-Rodríguez Francisco Ernesto, Ríos-Castro Emmanuel, Mondragón-Castelán Mónica Edith, González-Pozos Sirenia, Mondragón-Flores Ricardo

机构信息

Departamento de Bioquímica, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav), Av. IPN No. 2508, Ciudad de Mexico, C.P. 07360, Mexico.

Departamento de Infectómica y Patogénesis Molecular, Cinvestav, Mexico.

出版信息

J Proteomics. 2025 Oct 30;321:105509. doi: 10.1016/j.jprot.2025.105509. Epub 2025 Jul 25.

DOI:10.1016/j.jprot.2025.105509
PMID:40716488
Abstract

The Toxoplasma gondii cytoskeleton is a highly organized structure essential for parasite motility, replication, and host cell invasion. To identify its components, a highly enriched fraction of tachyzoite cytoskeletons was obtained and quantitatively analyzed by mass spectrometry. We identified 623 proteins classified into 18 functional groups, including 30 IMC proteins, 34 cytoskeleton proteins, and 14 uncharacterized proteins. A comprehensive bioinformatic analysis was conducted to assess protein abundance (fmol), antigenicity, accessibility, interactome, and homology, with the aim of identifying immunogenic targets. Among the top vaccine candidates were -GRA12, IMC1, ROP8, and -IMC4, with ROP8 emerging as the most promising based on epitope prediction. Data are available via ProteomeXchange with identifier PXD063409. SIGNIFICANCE: Toxoplasma gondii represents one of the most virulent and successful parasites in human and veterinary pathogenesis. Since T. gondii is a highly dynamic parasite that depends on its cytoskeleton to invade and disseminate through tissues, knowledge of its cytoskeleton composition is essential for understanding the biological mechanisms involved in parasite-host interactions and for the design of pharmaceutical and vaccination strategies. Quantitative proteomic analysis of the T. gondii cytoskeleton provided new and extensive information on its composition and, through bioinformatics approaches, allowed us to suggest several candidate molecules for future immunoprotective design.

摘要

刚地弓形虫的细胞骨架是一种高度有序的结构,对寄生虫的运动、复制和宿主细胞入侵至关重要。为了鉴定其组成成分,我们获得了高度富集的速殖子细胞骨架组分,并通过质谱进行了定量分析。我们鉴定出623种蛋白质,分为18个功能组,包括30种内膜复合体(IMC)蛋白、34种细胞骨架蛋白和14种未鉴定的蛋白质。进行了全面的生物信息学分析,以评估蛋白质丰度(飞摩尔)、抗原性、可及性、相互作用组和同源性,目的是鉴定免疫原性靶点。在最有潜力的疫苗候选物中,有-GRA12、IMC1、ROP8和-IMC4,基于表位预测,ROP8成为最有前景的候选物。数据可通过ProteomeXchange获得,标识符为PXD063409。意义:刚地弓形虫是人类和兽医发病机制中最具毒性和最成功的寄生虫之一。由于刚地弓形虫是一种高度动态的寄生虫,依赖其细胞骨架在组织中入侵和传播,了解其细胞骨架组成对于理解寄生虫与宿主相互作用所涉及的生物学机制以及设计药物和疫苗策略至关重要。对刚地弓形虫细胞骨架的定量蛋白质组学分析提供了关于其组成的新的广泛信息,并通过生物信息学方法,使我们能够为未来的免疫保护设计提出几种候选分子。

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