Plasmodium falciparum SURFIN4.1 forms an intermediate complex with PTEX components and Pf113 during export to the red blood cell
Plasmodium falciparum SURFIN4.1 forms an intermediate complex with PTEX components and Pf113 during export to the red blood cell
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恶性疟原虫 SURFIN4.1 在输出至红细胞期间与 PTEX 成分和 Pf113 形成中间复合物
DOI：
10.1016/j.parint.2021.102358
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发表时间：
2021
影响因子：
1.9
通讯作者：
Kaneko Osamu
中科院分区：
文献类型：
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作者：
Miyazaki Shinya;Chitama Ben-Yeddy Abel;Kagaya Wataru;Lucky Amuza Byaruhanga;Zhu Xiaotong;Yahata Kazuhide;Morita Masayuki;Takashima Eizo;Tsuboi Takafumi;Kaneko Osamu
恶性疟原虫将数百种蛋白质输出到受感染的红细胞（红细胞）的细胞质中，以改变适合其生长的细胞环境。输出蛋白的疟原虫转座（PTEX）是可溶性和整体膜蛋白穿过红细胞内寄生液泡（PV）膜所必需的。然而，整体膜蛋白易位复合物的分子组成尚未完全表征，特别是在寄生虫的质膜上。为了检查易位复合体，这里我们使用了mini-SURFIN4.1，由一个短n端区域、一个跨膜区域和一个输出的完整膜蛋白SURFIN4.1的细胞质区域组成。我们发现mini- surfin4.1与核心PTEX组分EXP2、HSP101和PTEX150形成一个易位中间复合物。我们还发现一些蛋白暴露于PV空间，包括Pf113，一种未表征的ptex相关蛋白。我们确定Pf113定位于分殖子期的致密颗粒中，以及红细胞入侵后的寄生虫外围。使用可诱导的跨位点堵塞的mini-SURFIN4.1，我们发现一个稳定的易位中间复合物在寄生虫质膜上形成，包含EXP2和Pf113的加工形式。这些结果表明Pf113可能在mini-SURFIN4.1的易位步骤中发挥作用，为寄生虫整体膜蛋白的易位机制提供了进一步的见解。
Plasmodium falciparummalaria parasites export several hundred proteins to the cytoplasm of infected red blood cells (RBCs) to modify the cell environment suitable for their growth. APlasmodiumtranslocon of exported proteins (PTEX) is necessary for both soluble and integral membrane proteins to cross the parasitophorous vacuole (PV) membrane surrounding the parasite inside the RBC. However, the molecular composition of the translocation complex for integral membrane proteins is not fully characterized, especially at the parasite plasma membrane. To examine the translocation complex, here we used mini-SURFIN4.1, consisting of a short N-terminal region, a transmembrane region, and a cytoplasmic region of an exported integral membrane protein SURFIN4.1. We found that mini-SURFIN4.1forms a translocation intermediate complex with core PTEX components, EXP2, HSP101, and PTEX150. We also found that several proteins are exposed to the PV space, including Pf113, an uncharacterized PTEX-associated protein. We determined that Pf113 localizes in dense granules at the merozoite stage and on the parasite periphery after RBC invasion. Using an inducible translocon-clogged mini-SURFIN4.1, we found that a stable translocation intermediate complex forms at the parasite plasma membrane and contains EXP2 and a processed form of Pf113. These results suggest a potential role of Pf113 for the translocation step of mini-SURFIN4.1, providing further insights into the translocation mechanisms for parasite integral membrane proteins.