Structural studies of the Apicomplexan glideosome-associated connector platform

顶端复合体滑翔体相关连接器平台的结构研究

• 批准号: BB/W001764/1
• 负责人: Steve Matthews
• 金额: $ 69.31万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FW001764%2F1
• 关键词: Structural; studies; Apicomplexan; glideosome; associated

A parasite grows in a different organism and while it is usually not a benefit to the host, it can often cause disease. The Apicomplexan parasites are single-celled, animal-like organisms which cause a range of diseases in humans and animals. Notably, Plasmodium falciparum is the chief cause of fatal malaria, while. Toxoplasma gondii, one of the world's most common parasites, and is of veterinary and medical importance, as it can cause abortion or congenital disease. It infects humans, wild and domestic animals, including birds, cats, sheep, goats, cattle, pigs and poultry. Toxoplasmosis has an enormous socio-economic and health impacts across the globe. Central to the survival of these parasite is their distinct ability to move (be motile), which allows them to target and invade host cells, live inside and subsequent escape. The molecular strategies that these parasite species employ to enter and escape their target cells are shared. An assembly of proteins form a molecular machine inside the parasite, known as the glideosome. A new protein, the glideosome-associated connector (GAC) has been recently discovered which represents a crucial molecular link between the host cell and the parasite cellular skeleton. This foothold allows the parasite to grip and move with respect to the host cell.This research project aims investigate the molecular shapes and interactions of the glideosome-associated connector (GAC) protein and define the architecture of this multi-component system. This information will help us to see at the atomic level how these parasites can move, and as this process is essential for parasite survival it will provide new guidance for the rational design of new vaccine strategies.

寄生虫在不同的生物体中生长，虽然它通常对宿主没有好处，但通常会引起疾病。 Apicomplexan寄生虫是单细胞的，类似动物的生物，会引起人类和动物的各种疾病。值得注意的是，恶性疟原虫是致命疟疾的主要原因。弓形虫弓形虫是世界上最常见的寄生虫之一，并且具有兽医和医学重要性，因为它可能导致堕胎或先天性疾病。它感染了人类，野生动物和家畜，包括鸟，猫，绵羊，山羊，牛，猪和家禽。弓形虫病在全球具有巨大的社会经济和健康影响。这些寄生虫生存的核心是它们移动的独特能力（Motile），这使他们能够靶向和入侵宿主细胞，生活在内部并随后逃脱。共享这些寄生虫物种进入和逃脱其靶细胞的分子策略。蛋白质的组装形成寄生虫内部的分子机，称为Glideosom。最近发现了一种新的蛋白质，与Glideosom相关的连接器（GAC），它代表了宿主细胞与寄生虫细胞骨架之间的关键分子联系。该立足点允许寄生虫抓住和移动相对于宿主细胞。该研究项目的目的是研究GlideoSome相关连接器（GAC）蛋白的分子形状和相互作用，并定义了该多组分系统的结构。这些信息将帮助我们在原子水平上查看这些寄生虫如何移动，并且由于此过程对于寄生虫生存至关重要，因此将为新的疫苗策略的合理设计提供新的指导。

项目成果

Structural and regulatory insights into the glideosome-associated connector from Toxoplasma gondii

对弓形虫滑翔体相关连接器的结构和监管见解

• DOI: 10.1101/2023.01.23.525158
• 发表时间: 2023
• 作者: Kumar A

Structural and regulatory insights into the glideosome-associated connector from Toxoplasma gondii.

• DOI: 10.7554/elife.86049
• 发表时间: 2023-04-04
• 期刊: eLife
• 影响因子: 7.7
• 作者: Kumar A;Vadas O;Dos Santos Pacheco N;Zhang X;Chao K;Darvill N;Rasmussen HØ;Xu Y;Lin GM;Stylianou FA;Pedersen JS;Rouse SL;Morgan ML;Soldati-Favre D;Matthews S
• 通讯作者: Matthews S