Truncation of merozoite surface protein 3 disrupts its trafficking and that of acidic-basic repeat protein to the surface of Plasmodium falciparum merozoites
Truncation of merozoite surface protein 3 disrupts its trafficking and that of acidic-basic repeat protein to the surface of Plasmodium falciparum merozoites
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DOI：
10.1046/j.1365-2958.2002.02834.x
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发表时间：
2002-03-01
影响因子：
3.6
通讯作者：
Cowman, AF
中科院分区：
文献类型：
--
作者：
Mills, KE;Pearce, JA;Cowman, AF
裂殖子表面蛋白3（MSP 3）是一种可溶性的恶性疟原虫裂殖子表面抗原，是一种重要的疫苗候选蛋白。MSP 3序列含有三个七肽重复序列，这与分子内卷曲螺旋的形成一致。MSP 3还含有富含谷氨酸的区域和在C-末端的推定亮氨酸拉链序列。我们已经破坏了msp 3基因的同源重组，导致MSP 3的截短形式的表达，缺乏推定的亮氨酸拉链序列，但保留了富含谷氨酸的区域和七肽重复序列。在这里，我们表明，截短的MSP 3，缺乏假定的亮氨酸拉链区，不本地化的寄生虫空泡或与裂殖子表面相互作用。此外，酸性-碱性重复抗原（ABRA），这是目前的裂殖子表面上，也没有本地化的merozolte表面的寄生虫表达的截短形式的MSP 3。表面缺乏MSP 3和ABRA的恶性疟原虫裂殖子表现出侵入红细胞的减少。这些结果表明，MSP 3是不是绝对必要的血液阶段的增长和假定的亮氨酸拉链区所需的运输MSP 3和ABRA的寄生虫空泡。
Merozoite surface protein 3 (MSP3), an important vaccine candidate, is a soluble polymorphic antigen associated with the surface of Plasmodium falciparum merozoites. The MSP3 sequence contains three blocks of heptad repeats that are consistent with the formation of an intramolecular coiled-coil. MSP3 also contains a glutamic acid-rich region and a putative leucine zipper sequence at the C-terminus. We have disrupted the msp3 gene by homologous recombination, resulting in the expression of a truncated form of MSP3 that lacks the putative leucine zipper sequence but retains the glutamic acid-rich region and the heptad repeats. Here, we show that truncated MSP3, lacking the putative leucine zipper region, does not localize to the parasitophorous vacuole or interact with the merozoite surface. Furthermore, the acidic-basic repeat antigen (ABRA), which is present on the merozoite surface, also was not localized to the merozolte surface in parasites expressing the truncated form of MSP3. The P falciparum merozoites lacking MSP3 and ABRA on the surface show reduced invasion into erythrocytes. These results suggest that MSP3 is not absolutely essential for blood stage growth and that the putative leucine zipper region is required for the trafficking of both MSP3 and ABRA to the parasitophorous vacuole.