The disruption of GDP-fucose de novo biosynthesis suggests the presence of a novel fucose-containing glycoconjugate in Plasmodium asexual blood stages.
The disruption of GDP-fucose de novo biosynthesis suggests the presence of a novel fucose-containing glycoconjugate in Plasmodium asexual blood stages.
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GDP量表从头生物合成的破坏表明，在疟原虫无性血液阶段中存在一种新型的含有纤维糖的糖缀合物。
DOI：
10.1038/srep37230
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发表时间：
2016-11-16
影响因子：
4.6
通讯作者：
Izquierdo L
中科院分区：
文献类型：
--
作者：
Sanz S;López-Gutiérrez B;Bandini G;Damerow S;Absalon S;Dinglasan RR;Samuelson J;Izquierdo L
糖基化是所有真核生物翻译后重要的蛋白质修饰。除了糖基磷脂酰肌醇（GPI）锚定位点和n -糖基化外，最近还报道了疟疾寄生虫关键孢子子蛋白的O-聚焦化。先前的分析表明，在恶性疟原虫的血液阶段存在GDP-聚焦（GDP- fuc），这是所有聚焦反应的前体。GDP-Fuc de novo途径需要gdp -甘露糖4,6-脱水酶（GMD）和GDP-L-聚焦合成酶（FS）的作用，在寄生虫基因组中是保守的，但聚焦代谢对寄生虫的重要性尚不清楚。为了对该通路进行功能表征，我们生成了PfGMD突变体并分析了其表型。虽然完全取消了焦点结合的欧洲巨鼠凝集素I （UEA-I）的标记，但在突变体中仍然检测到GDP-Fuc。这一意想不到的结果表明，存在一种维持寄生虫体内GDP-Fuc的替代机制。此外，PfGMD零突变体表现出正常的生长和侵袭率，这表明GDP-Fuc从头代谢途径在培养的疟原虫无性血期的发育中不是必需的。尽管如此，这一代谢途径和在这一阶段产生的GDP-Fuc库的功能可能对蚊子的配子细胞发生和孢子发育很重要。
Glycosylation is an important posttranslational protein modification in all eukaryotes. Besides glycosylphosphatidylinositol (GPI) anchors and N-glycosylation, O-fucosylation has been recently reported in key sporozoite proteins of the malaria parasite. Previous analyses showed the presence of GDP-fucose (GDP-Fuc), the precursor for all fucosylation reactions, in the blood stages of Plasmodium falciparum. The GDP-Fuc de novo pathway, which requires the action of GDP-mannose 4,6-dehydratase (GMD) and GDP-L-fucose synthase (FS), is conserved in the parasite genome, but the importance of fucose metabolism for the parasite is unknown. To functionally characterize the pathway we generated a PfGMD mutant and analyzed its phenotype. Although the labelling by the fucose-binding Ulex europaeus agglutinin I (UEA-I) was completely abrogated, GDP-Fuc was still detected in the mutant. This unexpected result suggests the presence of an alternative mechanism for maintaining GDP-Fuc in the parasite. Furthermore, PfGMD null mutant exhibited normal growth and invasion rates, revealing that the GDP-Fuc de novo metabolic pathway is not essential for the development in culture of the malaria parasite during the asexual blood stages. Nonetheless, the function of this metabolic route and the GDP-Fuc pool that is generated during this stage may be important for gametocytogenesis and sporogonic development in the mosquito.
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影响因子：
6.7
作者：
Cortés A;Carret C;Kaneko O;Yim Lim BY;Ivens A;Holder AA
通讯作者：
Holder AA
影响因子：
7
作者：
Lindner, Scott E.;Swearingen, Kristian E.;Kappe, Stefan H. I.
通讯作者：
Kappe, Stefan H. I.
影响因子：
--
作者：
Bushkin, G. Guy;Ratner, Daniel M.;Samuelson, John
通讯作者：
Samuelson, John
DOI：
10.1016/0005-2795(69)90193-7
发表时间：
1969-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
MATSUMOT.I;OSAWA, T
通讯作者：
OSAWA, T
影响因子：
1.5
作者：
Kirk, K;Horner, HA;Kirk, J
通讯作者：
Kirk, J