Molecular Analysis of PFEMP1 Binding Activity

PFEMP1 结合活性的分子分析

• 批准号: 6661263
• 负责人: JOSEPH D SMITH
• 金额: $ 31.33万
• 依托单位: SEATTLE BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6661263
• 关键词: CD antigens; Plasmodium falciparum; cell adhesion molecules; erythrocyte membrane; high throughput technology; host organism interaction; malaria; membrane proteins; microarray technology; pathologic process; protein structure function; receptor binding

DESCRIPTION: (provided by the applicant): It is estimated that Plasmodium falciparumkills one to two million people each year. While most infections are not lethal, severe disease occurs when infected erythrocytes sequester and accumulate in vital organs, such as brain and placenta. The P. falciparumerythrocyte membrane protein 1 (PfEMP1) family has a critical role in infected erythrocyte sequestration. PftMP1 are binding ligands that are exported to the erythrocyte surface. PfEMP1 have different binding specificity and are believed to determine the anatomic distribution of infected erythrocytes and disease outcome. To explore the role of PfEMP1 in malaria pathogenesis we will study three binding traits of infected erythrocytes, adhesion to CD36, to Intercellular adhesion molecule 1 (ICAM-1), and to chondroitin sulfate A (CSA) that have been implicated in malaria disease. CD36 is the major endothelial receptor for parasite sequestration. ICAM-1 and CSA have been implicated in cerebral and placental sequestration, respectively. PfEMP1 binding domains for each of these receptors have been defined. It is estimated that each parasite strain has approximately fifty different PfEMP1. We plan to perform whole genome surveys of PfEMPI binding, with high-throughput assays, focusing on the 3D7 parasite that is the subject of the Malaria Genome Project. Findings from these investigations will assess the extent to which binding properties are encoded and conserved between HEMP 1 in a genome and will provide insight into the pathogenic potential of P. falciparum.

描述：（由申请方提供）：据估计，疟原虫 每年有一百万到两百万人死于恶性疟原虫。虽然大多数感染是 当受感染的红细胞被隔离时， 在重要器官中积累，如大脑和胎盘。假单 恶性疟原虫红细胞膜蛋白1（PfEMP 1）家族在恶性疟原虫的发病机制中起重要作用。 感染的红细胞隔离。PftMP 1是结合配体， 输出到红细胞表面。PfEMP 1具有不同的结合特异性 并被认为决定了感染的解剖分布 红细胞和疾病结局。 为了探讨PfEMP 1在疟疾发病机制中的作用，我们将研究三种不同的基因， 感染红细胞的结合特性，与CD 36的粘附，与细胞间粘附 粘附分子1（ICAM-1）和硫酸软骨素A（CSA）， 与疟疾有关CD 36是内皮细胞的主要受体， 寄生虫隔离ICAM-1和CSA与脑缺血和脑梗死有关， 分别为胎盘隔离。PfEMP 1结合结构域， 受体已被确定。据估计，每种寄生虫菌株都有 大约50种不同的PfEMP 1。我们计划进行全基因组调查 PfEMPI结合，高通量测定，重点是3D 7寄生虫 这是疟疾基因组计划的主题。这些调查结果 研究将评估结合特性被编码的程度 并在基因组中HEMP 1之间保守，并将提供对HEMP 1的深入了解。 恶性疟原虫的致病潜力。