Suggestive Evidence for Darwinian Selection against Asparagine-Linked Glycans of Plasmodium falciparum and Toxoplasma gondii
Suggestive Evidence for Darwinian Selection against Asparagine-Linked Glycans of Plasmodium falciparum and Toxoplasma gondii
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DOI：
10.1128/ec.00197-09
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发表时间：
2010-02-01
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影响因子：
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通讯作者：
Samuelson, John
中科院分区：
文献类型：
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作者：
Bushkin, G. Guy;Ratner, Daniel M.;Samuelson, John
我们对恶性疟原虫和弓形虫的天冬酰胺连接的多糖(N-聚糖)很感兴趣，因为它们的N-聚糖结构一直存在争议，而且我们假设在核编码的蛋白质中可能存在针对N-聚糖的选择，这些蛋白质必须在进入质外体之前通过内质网(ER)。为了支持我们的假设，我们观察到了以下几点。首先，在有质外体的原生生物中，有大量的ALG酶的继发性损失，这些酶使N-糖链的脂质连接前体。泰勒氏菌不产生N-糖链，而疟原虫制造由一个或两个GlcNAc残基组成的严重截断的N-糖链前体。其次，弓形虫的分泌蛋白利用其自身的10糖前体(GLC(3)Man(5)GlcNAc(2))和宿主14糖前体(GLC(3)Man(9)GlcNAc(2))来制造N-糖基，N-糖基化位点很少，在其质膜靶标蛋白中有针对N-糖基的额外选择。第三，虽然GlcNAc结合的单叶灰树花凝集素II标记内质网、柱状体和原生质体表面，但没有质外体标记。同样，与弓形虫N-糖链结合的抗逆转录病毒凝集素氰化韦林-N标记内质网和棒状体，但没有质外体标记。我们的结论是，在具有质外体的原生生物中，针对N-糖链的可能选择是通过消除N-糖链(泰勒虫)、缩短其长度(疟原虫)或减少N-糖链位点的数量(弓形虫)来实现的。此外，与疟原虫和弓形虫中的某些分泌型蛋白相比，质外体蛋白中N-糖基的占有率显著降低。
We are interested in asparagine-linked glycans (N-glycans) of Plasmodium falciparum and Toxoplasma gondii, because their N-glycan structures have been controversial and because we hypothesize that there might be selection against N-glycans in nucleus-encoded proteins that must pass through the endoplasmic reticulum (ER) prior to threading into the apicoplast. In support of our hypothesis, we observed the following. First, in protists with apicoplasts, there is extensive secondary loss of Alg enzymes that make lipid-linked precursors to N-glycans. Theileria makes no N-glycans, and Plasmodium makes a severely truncated N-glycan precursor composed of one or two GlcNAc residues. Second, secreted proteins of Toxoplasma, which uses its own 10-sugar precursor (Glc(3)Man(5)GlcNAc(2)) and the host 14-sugar precursor (Glc(3)Man(9)GlcNAc(2)) to make N-glycans, have very few sites for N glycosylation, and there is additional selection against N-glycan sites in its apicoplast-targeted proteins. Third, while the GlcNAc-binding Griffonia simplicifolia lectin II labels ER, rhoptries, and surface of plasmodia, there is no apicoplast labeling. Similarly, the antiretroviral lectin cyanovirin-N, which binds to N-glycans of Toxoplasma, labels ER and rhoptries, but there is no apicoplast labeling. We conclude that possible selection against N-glycans in protists with apicoplasts occurs by eliminating N-glycans (Theileria), reducing their length (Plasmodium), or reducing the number of N-glycan sites (Toxoplasma). In addition, occupation of N-glycan sites is markedly reduced in apicoplast proteins versus some secretory proteins in both Plasmodium and Toxoplasma.