A Family of Dual-Activity Glycosyltransferase-Phosphorylases Mediates Mannogen Turnover and Virulence in Leishmania Parasites.
A Family of Dual-Activity Glycosyltransferase-Phosphorylases Mediates Mannogen Turnover and Virulence in Leishmania Parasites.
复制标题
DOI：
10.1016/j.chom.2019.08.009
复制
发表时间：
2019-09
影响因子：
30.3
通讯作者：
M. F. Sernee;J. Ralton;T. Nero;Lukasz F Sobala;Joachim Kloehn;Marcel A. Vieira-Lara;Simon A. Cobbold;L. Stanton;D. Pires;E. Hanssen;A. Males;T. Ward;L. M. Bastidas;Phillip L van der Peet;M. Parker;D. Ascher;Spencer J. Williams;G. Davies;M. McConville
中科院分区：
文献类型：
--
作者：
M. F. Sernee;J. Ralton;T. Nero;Lukasz F Sobala;Joachim Kloehn;Marcel A. Vieira-Lara;Simon A. Cobbold;L. Stanton;D. Pires;E. Hanssen;A. Males;T. Ward;L. M. Bastidas;Phillip L van der Peet;M. Parker;D. Ascher;Spencer J. Williams;G. Davies;M. McConville
属于利什曼原虫属的寄生原生生物合成非典型碳水化合物储备甘露原，它由β-1,2-甘露寡糖组成。在这里，我们鉴定了一类双活性甘露糖基转移酶/磷酸化酶 (MTP)，其催化糖核苷酸依赖性生物合成和甘露原的磷酸解转换。结构和系统发育分析表明，虽然 MTP 在结构上与细菌甘露聚糖磷酸化酶相关，但它们构成了一个独特的糖基转移酶 (GT108) 家族，该家族可能是通过革兰氏阳性细菌的水平基因转移获得的。七个 MTP 催化甘露原的组成型合成和周转。这种代谢变阻器可保护专性细胞内寄生虫阶段免受营养过剩的影响，对于哺乳动物宿主的耐热性和寄生虫感染性至关重要。我们的结果表明，MTP 家族在利什曼原虫中的获得和扩展增加了这些原生生物的代谢灵活性，并有助于它们殖民新宿主生态位的能力。
Parasitic protists belonging to the genusLeishmaniasynthesize the non-canonical carbohydrate reserve, mannogen, which is composed of β-1,2-mannan oligosaccharides. Here, we identify a class of dual-activity mannosyltransferase/phosphorylases (MTPs) that catalyze both the sugar nucleotide-dependent biosynthesis and phosphorolytic turnover of mannogen. Structural and phylogenic analysis shows that while the MTPs are structurally related to bacterial mannan phosphorylases, they constitute a distinct family of glycosyltransferases (GT108) that have likely been acquired by horizontal gene transfer from gram-positive bacteria. The seven MTPs catalyze the constitutive synthesis and turnover of mannogen. This metabolic rheostat protects obligate intracellular parasite stages from nutrient excess, and is essential for thermotolerance and parasite infectivity in the mammalian host. Our results suggest that the acquisition and expansion of the MTP family inLeishmaniaincreased the metabolic flexibility of these protists and contributed to their capacity to colonize new host niches.