Lee Sungsu, Cheung-See-Kit Melanie, Williams Tyler A, Yamout Nader, Zufferey Rachel
Department of Biological Sciences, St John's University, 8000 Utopia Parkway, Jamaica, NY 11439, USA.
Department of Biological Sciences, St John's University, 8000 Utopia Parkway, Jamaica, NY 11439, USA.
Exp Parasitol. 2018 Feb;185:71-78. doi: 10.1016/j.exppara.2018.01.014.
Glycerophospholipids are the main constituents of the biological membranes in Trypanosoma brucei, which causes sleeping sickness in humans. The present work reports the characterization of the alkyl-dihydroxyacetonephosphate synthase TbADS that catalyzes the committed step in ether glycerophospholipid biosynthesis. TbADS localizes to the glycosomal lumen. TbADS complemented a null mutant of Leishmania major lacking alkyl-dihydroxyacetonephosphate synthase activity and restored the formation of normal form of the ether lipid based virulence factor lipophosphoglycan. Despite lacking alkyl-dihydroxyacetonephosphate synthase activity, a null mutant of TbADS in procyclic trypanosomes remained viable and exhibited normal growth. Comprehensive analysis of cellular glycerophospholipids showed that TbADS was involved in the biosynthesis of all ether glycerophospholipid species, primarily found in the PE and PC classes.
甘油磷脂是布氏锥虫生物膜的主要成分,布氏锥虫可导致人类患昏睡病。目前的研究报告了烷基二羟基丙酮磷酸合酶TbADS的特性,该酶催化醚甘油磷脂生物合成中的关键步骤。TbADS定位于糖体腔。TbADS补充了缺乏烷基二羟基丙酮磷酸合酶活性的大利什曼原虫的无效突变体,并恢复了基于醚脂的毒力因子脂磷壁酸正常形式的形成。尽管缺乏烷基二羟基丙酮磷酸合酶活性,但前循环锥虫中TbADS的无效突变体仍能存活并表现出正常生长。对细胞甘油磷脂的综合分析表明,TbADS参与了所有醚甘油磷脂种类的生物合成,主要存在于PE和PC类别中。