TRANSPORT PROPERTIES OF CRYPTOSPORIDIUM PARVUM CPABC

小隐孢子虫 CPABC 的运输特性

• 批准号: 6147603
• 负责人: SYLVIA M LEBLANCQ
• 金额: $ 33.85万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-15 至 2001-04-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6147603
• 关键词: Baculoviridae; Cryptosporidium; FK506; Saccharomyces cerevisiae; Sf9 cell line; adenosinetriphosphatase; biological transport; cadmium; chloramphenicol; cryptosporidiosis; drug resistance; enzyme activity; fluconazole; metal metabolism; microorganism metabolism; molecular cloning; oligomycins; recombinant proteins; transport proteins; vanadium

Cryptosporidium parvum is an important opportunistic infection in persons with the acquired immunodeficiency syndrome (AIDS). C. parvum is an intracellular parasite that invades epithelial cells in the gastrointestinal tract where it develops inside a vacuole at the apex of the host cell. Intracellular parasites must obtain nutrients from the host cell, and these materials have to cross the membrane(s) of the host-parasite boundary. The transport pathways essential for parasite development are poorly understood in C. parvum. The major host-parasite interface in C. parvum-infected cells is an extensively folded membranous structure known as the feeder organelle. CpABC is a C. parvum ATP-binding cassette (ABC) transporter protein localized to the feeder organelle region. CpABC is the first transporter to be identified in C. parvum, and it is the first protein to be localized to the feeder organelle region. CpABC shares conserved features of protein structure with the multidrug resistance protein (MRF) subfamily of ABC transporter proteins. The structure and location of CpABC suggests that it plays an important role in the regulation of transport in the developing parasite. The objective of this proposal is to elucidate the transport properties of CpABC. This will be accomplished through the use of two tractable model systems: the baculovirus-insect cell expression system and the yeast Saccharomyces cerevisiae. The aims are: 1) to characterize CpABC biochemically by the analysis of ATPase and transport activities. 2) to characterize CpABC by functional analyses in yeast. The long term goal is to understand the physiological role of CpABC and the functioning of the feeder organelle.

在患有免疫缺陷综合征（AIDS）的人中，隐孢子虫是一种重要的机会感染。 C. parvum是一种细胞内寄生虫，它侵入胃肠道中的上皮细胞，在宿主细胞顶点的液泡内发育。细胞内寄生虫必须从宿主细胞中获得营养，这些材料必须越过宿主 - 寄生虫边界的膜。在C. parvum中，对寄生虫发育必不可少的运输途径了解不足。 C. parvum感染的细胞中的主要宿主寄生虫界面是一种被称为馈线细胞器的广泛折叠的膜结构。 CPABC是C. parvum ATP结合盒（ABC）转运蛋白蛋白质位于馈线细胞器区域。 CPABC是第一个在Parvum中鉴定的转运蛋白，它是第一个定位于进料机细胞器区域的蛋白质。 CPABC与ABC转运蛋白的多药耐药蛋白（MRF）共享蛋白质结构的保守特征。 CPABC的结构和位置表明，它在发育中的寄生虫的运输调节中起着重要作用。该提案的目的是阐明CPABC的运输特性。这将通过使用两个可触及的模型系统来实现：杆状病毒诱导的细胞表达系统和酵母菌酿酒酵母。目的是：1）通过对ATPase和运输活动的分析来表征CPABC生化。 2）通过酵母中的功能分析来表征CPABC。长期目标是了解CPABC的生理作用和馈线细胞器的功能。