The assembly of multimeric protein complexes in the sexual stages of the human malaria parasite Plasmodium falciparum

人类疟原虫恶性疟原虫性阶段多聚蛋白复合物的组装

• 批准号: 204233715
• 负责人: Professorin Dr. Gabriele Pradel
• 金额: --
• 依托单位: Abteilung für Zelluläre und Angewandte Infektionsbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/204233715?language=en
• 关键词: assembly; multimeric; protein; complexes; sexual

Sexual reproduction of the malaria parasite is initiated following its transmission from the human host to the mosquito vector during a blood meal. The sexual stages are the only life-cycle stages of the parasite that are able to establish an infection in the mosquito and thus play an important role for spread of the tropical disease. Parasite transmission is mediated by sexual precursor cells, the gametocytes, that in the midgut of the mosquito transform into fertile gametes. During gametocyte differentiation, a high number of surface-associated adhesion proteins are expressed, which assemble to multimeric protein complexes (MPCs) and which are subsequently exposed on the gamete surface. Antibodies directed against MPC proteins result in complement-mediated lysis of sexual stage parasites in the mosquito midgut, thereby blocking further development of the parasite in the vector. MPC proteins therefore represent promising candidates for transmission blocking vaccines. MPCs are multifunctional units mediating contact of sexual stage parasites and possibly play a role in gametogenesis as well as in finding and fusion of mating partners. The assembly of MPCs and their fate during parasite development in the mosquito midgut, however, are up to date not well understood. It is therefore the aim of this proposal to investigate the molecular composition of sexual stage MPCs, to identify a possible connection of MPCs with the submembranous elements of the gametocyte cytoskeleton and to investigate processing, relocation and degradation of MPC proteins.

疟疾寄生虫在血餐期间从人类宿主传播到蚊子媒介后开始有性繁殖。性阶段是寄生虫的唯一生命周期阶段，能够在蚊子中建立感染，从而在热带疾病的传播中发挥重要作用。寄生虫的传播是由性前体细胞介导的，即蚊子中肠的配子体，这些配子体转化为可育的配子。在配子体分化过程中，大量的表面相关黏附蛋白被表达，这些黏附蛋白聚集成多聚体蛋白复合体(MPC)，随后暴露在配子表面。针对MPC蛋白的抗体导致补体介导的有性期蚊子中肠寄生虫的裂解，从而阻止寄生虫在媒介中的进一步发展。因此，MPC蛋白是传播阻断疫苗的有前途的候选者。MPC是介导有性期寄生虫接触的多功能单位，可能在配子发生以及寻找和融合交配伙伴方面发挥作用。然而，到目前为止，对MPC的组装及其在蚊子中肠寄生虫发育过程中的命运还没有很好的了解。因此，这项建议的目的是研究有性阶段MPC的分子组成，确定MPC与配子体细胞骨架亚膜元件的可能联系，并研究MPC蛋白的加工、重新定位和降解。