Export of malaria proteins requires co-translational processing of the PEXEL motif independent of phosphatidylinositol-3-phosphate binding.
Export of malaria proteins requires co-translational processing of the PEXEL motif independent of phosphatidylinositol-3-phosphate binding.
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DOI：
10.1038/ncomms10470
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发表时间：
2016-02-01
影响因子：
16.6
通讯作者：
Cowman AF
中科院分区：
文献类型：
--
作者：
Boddey JA;O'Neill MT;Lopaticki S;Carvalho TG;Hodder AN;Nebl T;Wawra S;van West P;Ebrahimzadeh Z;Richard D;Flemming S;Spielmann T;Przyborski J;Babon JJ;Cowman AF
恶性疟原虫利用疟原虫输出元件 (PEXEL) 基序将蛋白质输出到红细胞中，该基序在内质网 (ER) 中被血浆蛋白酶 V (PMV) 切割。最近的一项研究报道，集中在 ER 中的磷脂酰肌醇-3-磷酸 (PI(3)P) 与 PEXEL 基序结合，并且是独立于 PMV 输出所需的，并且 PEXEL 基序在功能上可与卵菌效应子的 RxLR 基序互换。在这里，我们表明 PEXEL 不结合 PI(3)P，并且这种脂质不浓缩在 ER 中。我们发现 RxLR 基序不能介导恶性疟原虫中的输出。表达 KAHRP 突变版本的寄生虫（PEXEL 基序重新定位在信号序列附近）可阻止 PMV 裂解。该突变体具有假定的 PI(3)P 结合残基，但不输出。将 PEXEL 恢复到其原始位置可恢复 PMV 的处理和导出。这些结果挑战了 PI(3)P 假说，并提供了 PEXEL 位置对于共翻译处理和导出而言是保守的证据。 将恶性疟原虫蛋白输出到受感染的红细胞中依赖于目标蛋白中的 PEXEL 基序。这里是博迪等人。对 PEXEL 基序通过结合 PI(3)P 介导输出的假设提出质疑，转而表明它通过 plasmepsin V 的切割发挥作用。
Plasmodium falciparum exports proteins into erythrocytes using the Plasmodium export element (PEXEL) motif, which is cleaved in the endoplasmic reticulum (ER) by plasmepsin V (PMV). A recent study reported that phosphatidylinositol-3-phosphate (PI(3)P) concentrated in the ER binds to PEXEL motifs and is required for export independent of PMV, and that PEXEL motifs are functionally interchangeable with RxLR motifs of oomycete effectors. Here we show that the PEXEL does not bind PI(3)P, and that this lipid is not concentrated in the ER. We find that RxLR motifs cannot mediate export in P. falciparum. Parasites expressing a mutated version of KAHRP, with the PEXEL motif repositioned near the signal sequence, prevented PMV cleavage. This mutant possessed the putative PI(3)P-binding residues but is not exported. Reinstatement of PEXEL to its original location restores processing by PMV and export. These results challenge the PI(3)P hypothesis and provide evidence that PEXEL position is conserved for co-translational processing and export. Export of Plasmodium falciparum proteins into infected erythrocytes relies upon the PEXEL motif in target proteins. Here Boddey et al. challenge the hypothesis that the PEXEL motif mediates export by binding PI(3)P and instead suggest it acts via cleavage by plasmepsin V.