PROTEIN TARGETING TO AND THROUGH THE T GONDII PVM

靶向并通过 T GONDII PVM 的蛋白质

• 批准号: 2718675
• 负责人: KEITH Alan JOINER
• 金额: $ 2.52万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2001-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2718675
• 关键词: AIDS; Plasmodium falciparum; Toxoplasma gondii; binding proteins; chimeric proteins; intracellular parasitism; membrane proteins; opportunistic infections; protein localization; protein structure function; protein transport; tissue /cell culture; vesicle /vacuole

DESCRIPTION (adapted from the ABSTRACT): Toxoplasma gondii is the leading cause of local central nervous system infections in patients with AIDS. T. gondii is a member of the apicomplexan family of parasites, which includes crytosporidium and plasmodium species, all of which are obligate intracellular parasites. For Toxoplasma and Plasmodia, the vacuole is surrounded by a specialized membrane, termed the parasitophorous vacuole membrane (PVM), which is the interface between the parasite and the host cell. Although selected characteristics of the T. gondii PVM are understood, other features are more well defined and/or easier to study in plasmodium-infected erythrocytes. In particular, the biosynthesis, transport, and subsequent topology of the transmembrane protein EXP-1 within the P. falciparum PVM is established, and is the transport of a subset of soluble proteins (including glycophorin-binding protein, or GBP) across the PVM and into the erythrocyte cytosol. To facilitate our understanding of the T. gondii PVM, using tools developed to study P. falciparum-infected erythrocytes, the Investigator proposes to: (1) identify the topology of EXP-1 expressed in Toxoplasma and determine the subcellular localization and transport of the protein in T. gondii- infected cells, and (2) identify T. gondii proteins which are transported across the PVM and into the host cell cytosol and explore the mechanism for this process. These experiment will simultaneously provide insight into the structure and function of the T. gondii PVM and will delineate both the similarities and differences between the PVM in the two parasites. This collaboration between a U.S. laboratory with expertise in T. gondii biology and a german laboratory with expertise in Plasmodia biology will foster our understanding of the PVM of both parasites and have implication for drug delivery into the intracellular organisms.

描述（改编自摘要）：弓形虫是 导致艾滋病患者局部中枢神经系统感染。T. 弓形虫是顶复门寄生虫家族的成员，包括 隐孢子虫和疟原虫物种，所有这些都是专性的 细胞内寄生虫对于弓形虫和疟原虫，空泡是 被一种特殊的膜包围，称为寄生泡 膜（PVM），这是寄生虫和宿主之间的界面 cell.虽然T.弓形虫PVM 在理解中，其他特征更好地定义和/或更容易研究， 疟原虫感染的红细胞特别是生物合成， 跨膜蛋白EXP-1的转运和随后的拓扑结构 在恶性疟原虫PVM内建立，并且是 可溶性蛋白亚类（包括血型糖蛋白结合蛋白，或GBP） 穿过PVM进入红细胞胞质。促进我们 对T. gondii PVM，使用开发的工具来研究P. 恶性疟原虫感染的红细胞，研究者建议：（1） 鉴定在弓形虫中表达的EXP-1的拓扑结构，并确定 该蛋白在T.弓形虫， 感染的细胞;（2）鉴定T.被运输的弓形虫蛋白 通过PVM进入宿主细胞胞浆并探讨其机制 for this process过程.这些实验将同时提供 T的结构和功能弓形虫PVM和将描绘 两者之间的异同PVM在两个 寄生虫这是一个美国实验室与专业知识， T.弓形虫生物学和一个专门研究疟原虫的德国实验室 生物学将促进我们对寄生虫PVM的理解， 具有将药物递送到细胞内生物体中的含义。