Processing of Plasmodium falciparum Merozoite Surface Protein MSP1 Activates a Spectrin-Binding Function Enabling Parasite Egress from RBCs.
Processing of Plasmodium falciparum Merozoite Surface Protein MSP1 Activates a Spectrin-Binding Function Enabling Parasite Egress from RBCs.
复制标题
加工恶性疟原虫梅罗唑群体表面蛋白MSP1激活谱线结合功能，从而使RBC的寄生虫出口。
DOI：
10.1016/j.chom.2015.09.007
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发表时间：
2015-10-14
影响因子：
30.3
通讯作者：
Blackman MJ
中科院分区：
文献类型：
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作者：
Das S;Hertrich N;Perrin AJ;Withers-Martinez C;Collins CR;Jones ML;Watermeyer JM;Fobes ET;Martin SR;Saibil HR;Wright GJ;Treeck M;Epp C;Blackman MJ
恶性疟原虫在红细胞内复制，产生后代裂殖子，这些裂殖子通过一种鲜为人知的称为出口的过程从感染细胞中释放出来。最丰富的裂殖子表面蛋白，MSP 1，合成为一个大的前体，经历蛋白水解成熟的寄生虫蛋白酶SUB1之前出口。MSP1的功能及其处理是未知的。在这里，我们表明，SUB1介导的加工MSP1是重要的寄生虫的生存能力。加工修饰MSP 1的二级结构并激活其结合血影蛋白的能力，血影蛋白是宿主红细胞细胞骨架的主要成分的分子支架蛋白。表达低效加工的MSP 1突变体的寄生虫表现出延迟的排出，而缺乏表面结合的MSP 1的裂殖子则表现出严重的排出缺陷。我们的研究结果表明，SUB1处理裂殖子表面MSP 1和血影蛋白网络的红细胞骨架之间的相互作用，促进宿主红细胞破裂，使寄生虫出口。裂殖子表面蛋白MSP1的加工对恶性疟原虫的生存能力是重要的蛋白水解加工激活MSP1的肝素和血影蛋白结合功能MSP1加工的速率控制寄生虫排出的动力学寄生虫表面MSP1的丢失导致严重的排出缺陷从受感染的红细胞排出是疟疾寄生虫生命周期中的关键步骤，但人们对这一步骤的了解很少。Das等人报道，就在排出之前，寄生虫表面蛋白MSP 1的蛋白水解处理激活血影蛋白结合功能，允许细胞内寄生虫与RBC细胞骨架相互作用并使其能够排出。
The malaria parasite Plasmodium falciparum replicates within erythrocytes, producing progeny merozoites that are released from infected cells via a poorly understood process called egress. The most abundant merozoite surface protein, MSP1, is synthesized as a large precursor that undergoes proteolytic maturation by the parasite protease SUB1 just prior to egress. The function of MSP1 and its processing are unknown. Here we show that SUB1-mediated processing of MSP1 is important for parasite viability. Processing modifies the secondary structure of MSP1 and activates its capacity to bind spectrin, a molecular scaffold protein that is the major component of the host erythrocyte cytoskeleton. Parasites expressing an inefficiently processed MSP1 mutant show delayed egress, and merozoites lacking surface-bound MSP1 display a severe egress defect. Our results indicate that interactions between SUB1-processed merozoite surface MSP1 and the spectrin network of the erythrocyte cytoskeleton facilitate host erythrocyte rupture to enable parasite egress. Merozoite surface protein MSP1 processing is important for P. falciparum viability Proteolytic processing activates MSP1’s heparin and spectrin-binding functions The rate of MSP1 processing governs the kinetics of parasite egress Loss of parasite surface MSP1 results in a severe egress defect Egress from infected RBCs is a critical, but poorly understood, step in the malaria parasite’s lifecycle. Das et al. report that just prior to egress, proteolytic processing of parasite surface protein MSP1 activates a spectrin binding function, allowing the intracellular parasite to interact with the RBC cytoskeleton and enabling egress.