Division of Molecular Microbiology and Immunology, CSIR-Central Drug Research Institute, Lucknow 226031, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
ACS Infect Dis. 2024 Apr 12;10(4):1116-1125. doi: 10.1021/acsinfecdis.3c00631. Epub 2024 Feb 29.
The O-fucosylation of the thrombospondin type I repeat (TSR) domain is important for TSR-containing proteins' optimal folding and stability. However, the importance of O-fucosyltransferase 2 (POFut2) remains unclear due to two different reports. Here, we disrupted the gene in and demonstrated that KO parasites develop normally in blood and mosquito stages but show reduced infectivity in mice. We found that the reduced infectivity of KO sporozoites was due to a diminished level of TRAP that affected the parasite gliding motility and hepatocyte infectivity. Using all-atom MD simulation, we also hypothesize that O-fucosylation impacts the TSR domain's stability more than its heparin binding capacity.
O-岩藻糖基化在富含血栓反应蛋白型 I 重复(TSR)结构域的蛋白质的正确折叠和稳定性中起着重要作用。然而,由于有两个不同的报道,O-岩藻糖基转移酶 2(POFut2)的重要性仍不清楚。在这里,我们敲除了 和 中的 基因,并证明 基因敲除的疟原虫在血液和蚊子阶段正常发育,但在小鼠中的感染性降低。我们发现, 基因敲除的子孢子的感染性降低是由于 TRAP 水平降低,这影响了寄生虫的滑行运动和肝细胞感染性。通过全原子 MD 模拟,我们还假设 O-岩藻糖基化对 TSR 结构域的稳定性的影响大于其对肝素结合能力的影响。