Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India.
Medicinal Chemistry Laboratory, Department of Biosciences, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi, India.
FEBS Open Bio. 2022 May;12(5):1050-1060. doi: 10.1002/2211-5463.13022. Epub 2022 Mar 29.
Malaria is a human disease caused by eukaryotic protozoan parasites of the Plasmodium genus. Plasmodium falciparum (Pf) causes the most lethal form of human malaria and is responsible for widespread mortality worldwide. Prefoldin is a heterohexameric molecular complex that binds and delivers unfolded proteins to chaperonin for correct folding. The prefoldin PFD6 is predicted to interact with merozoite surface protein-1 (MSP-1), a protein well known to play a pivotal role in erythrocyte binding and invasion by Plasmodium merozoites. We previously found that the P. falciparum (Pf) genome contains six prefoldin genes and a prefoldin-like gene whose molecular functions are unidentified. Here, we analyzed the expression of PfPFD-6 during the asexual blood stages of the parasite and investigated its interacting partners. PfPFD-6 was found to be significantly expressed at the trophozoite and schizont stages. Pull-down assays suggest PfPFD-6 interacts with MSP-1. In silico analysis suggested critical residues involved in the PfPFD-6-MSP-1 interaction. Our data suggest PfPFD-6 may play a role in stabilizing or trafficking MSP-1.
疟疾是一种由疟原虫属的真核原生动物寄生虫引起的人类疾病。疟原虫 恶性疟原虫（Pf）可引起最致命的人类疟疾，是全球广泛死亡的罪魁祸首。原初折叠酶是一种异六聚体分子复合物，可结合和递呈未折叠的蛋白质给伴侣蛋白以进行正确折叠。原初折叠酶 PFD6 被预测与裂殖子表面蛋白-1（MSP-1）相互作用，MSP-1 是一种众所周知的在疟原虫裂殖子与红细胞结合和入侵过程中起关键作用的蛋白。我们之前发现，恶性疟原虫（Pf）基因组包含六个原初折叠酶基因和一个原初折叠酶样基因，但其分子功能尚未确定。在这里，我们分析了 PfPFD-6 在寄生虫无性血期的表达情况，并研究了其相互作用的伙伴。PfPFD-6 在滋养体和裂殖体阶段表达水平显著。下拉实验表明 PfPFD-6 与 MSP-1 相互作用。计算机分析表明 PfPFD-6 与 MSP-1 相互作用的关键残基。我们的数据表明 PfPFD-6 可能在稳定或运输 MSP-1 方面发挥作用。
