Functional and phylogenetic evidence of a bacterial origin for the first enzyme in sphingolipid biosynthesis in a phylum of eukaryotic protozoan parasites.
Functional and phylogenetic evidence of a bacterial origin for the first enzyme in sphingolipid biosynthesis in a phylum of eukaryotic protozoan parasites.
复制标题
DOI：
10.1074/jbc.m117.792374
复制
发表时间：
2017-07-21
期刊：
影响因子：
--
通讯作者：
Denny PW
中科院分区：
文献类型：
--
作者：
Mina JG;Thye JK;Alqaisi AQI;Bird LE;Dods RH;Grøftehauge MK;Mosely JA;Pratt S;Shams-Eldin H;Schwarz RT;Pohl E;Denny PW
刚地弓形虫是一种专性、细胞内真核顶端复合体原生动物寄生虫，可导致动物和人类的胎儿损伤和流产。鞘脂是真核生物膜的基本和普遍成分，由顶复合体合成和清除。在这里，我们报道了弓形虫丝氨酸棕榈酰转移酶的鉴定、分离和分析，这种酶催化鞘脂生物合成的第一步和限速步骤：丝氨酸和棕榈酰辅酶a的缩合。在迄今为止分析的所有真核生物中，丝氨酸棕榈酰转移酶是一种高度保守的异二聚体酶复合物。然而，生化和结构分析表明，顶复合体同源物是一种功能性的、同源二聚体的丝氨酸棕榈酰转移酶，定位于内质网。此外，系统发育研究表明，它与鞘单胞菌科原核丝氨酸棕榈酰基转移酶（一种可溶性同型二聚体酶）进化相关。因此，这种酶在整个顶复合体中都是保守的，很可能是通过原核生物的横向基因转移获得的。
Toxoplasma gondii is an obligate, intracellular eukaryotic apicomplexan protozoan parasite that can cause fetal damage and abortion in both animals and humans. Sphingolipids are essential and ubiquitous components of eukaryotic membranes that are both synthesized and scavenged by the Apicomplexa. Here we report the identification, isolation, and analyses of the Toxoplasma serine palmitoyltransferase, an enzyme catalyzing the first and rate-limiting step in sphingolipid biosynthesis: the condensation of serine and palmitoyl-CoA. In all eukaryotes analyzed to date, serine palmitoyltransferase is a highly conserved heterodimeric enzyme complex. However, biochemical and structural analyses demonstrated the apicomplexan orthologue to be a functional, homodimeric serine palmitoyltransferase localized to the endoplasmic reticulum. Furthermore, phylogenetic studies indicated that it was evolutionarily related to the prokaryotic serine palmitoyltransferase, identified in the Sphingomonadaceae as a soluble homodimeric enzyme. Therefore this enzyme, conserved throughout the Apicomplexa, is likely to have been obtained via lateral gene transfer from a prokaryote.