熱帯熱マラリア原虫のSURFIN4.1の赤血球への効率的な輸送にはN末端領域の複数の荷電アミノ酸が重要である

Abstract

Plasmodium falciparum, an obligate intracellular protozoan parasite which causes the severe form of human malaria, exports numerous proteins to the infected red blood cell that are important for its survival and of severe pathological effect to its host. These proteins and their export mechanisms are candidates for drug and vaccine development, and among them is the Plasmodium SURFIN family of proteins. Previously we showed that the N-terminal region along with the sequence surrounding the transmembrane domain of SURFIN4.1 is essential for its export to Maurer\u27s clefts in the red blood cell cytoplasm. We proposed that this region is recognized by a machinery responsible for protein translocation across the parasitophorous vacuole membrane surrounding the parasite. To understand the export mechanism further, we utilized a fluorescent protein-tagged mini-SURFIN4.1 consisting of the minimum essential components for export. Alanine scanning of all charged amino acids within the N-terminal region revealed that replacement of 3 glutamic acid and 2 lysine residues significantly impairs the export efficiency of this protein across the parasitophorous vacuole membrane. In addition, N-terminally Myc-tagged mini-SURFIN4.1 and mini-SURFIN4.2 with similar architectures were detected with anti-Myc antibody at Maurer\u27s clefts, indicating that elements required for export to Maurer\u27s clefts are conserved between SURFIN4.1 and SURFIN4.2, and that N-terminal sequences of these SURFIN members are not cleaved during export. Our results implicate a conserved nature of SURFIN export to the red blood cell, particularly an important role of multiple glutamic acid and lysine residues in the SURFIN N-terminal region.長崎大学学位論文 学位記番号:博(医歯薬)甲第1171号 学位授与年月日:令和元年6月5日Author: Ben-Yeddy Abel Chitama, Shinya Miyazaki, Xiaotong Zhu, Wataru Kagaya, Kazuhide Yahata, Osamu KanekoCitation: Parasitology International, 71, pp.186-193; 2019Nagasaki University (長崎大学)課程博