A subtilisin-like protein in secretory organelles of Plasmodium falciparum merozoites

A subtilisin-like protein in secretory organelles of Plasmodium falciparum merozoites
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DOI:
10.1074/jbc.273.36.23398
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发表时间:
1998-09-04
影响因子:
4.8
通讯作者:
Hackett, F
Hackett, F
中科院分区:
生物学2区
文献类型:
--
作者:
Blackman, MJ;Fujioka, H;Hackett, F

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在脊椎动物宿主中,疟原虫侵入并在循环红细胞内无性复制。寄生虫蛋白水解酶在红细胞侵袭中起重要作用,但了解甚少。我们已经确定了恶性疟原虫基因,表示pf-sub-1,编码枯草杆菌蛋白酶样丝氨酸蛋白酶家族(枯草杆菌酶)的成员。Pfsub-1基因在恶性疟原虫的无性血液阶段表达,并且初级基因产物(Pfsub-1)在分泌运输期间以与其转化为成熟的酶活性形式一致的方式经历翻译后加工,如对其他枯草杆菌酶所记录的。在侵入性裂殖子中,假定的成熟蛋白酶(p47)集中在致密颗粒中,这些颗粒是位于裂殖子顶端的分泌细胞器。在裂殖子释放和红细胞侵入完成后的某个时间点,p47以截短的可溶形式从寄生虫分泌。p47的亚细胞定位和分泌时间表明,它可能在红细胞侵袭中发挥作用。Pfizer-1是抗疟药物开发的一个新的潜在靶点。
In the vertebrate host, the malaria parasite invades and replicates asexually within circulating erythrocytes. Parasite proteolytic enzymes play an essential but poorly understood role in erythrocyte invasion. We have identified a Plasmodium falciparum gene, denoted pf-sub-1, encoding a member of the subtilisin-like serine protease family (subtilases). The pfsub-1 gene is ex pressed in asexual blood stages of P. falciparum, and the primary gene product (PfSUB-1) undergoes post-translational processing during secretory transport in a manner consistent with its being converted to a mature, enzymatically active form, as documented for other subtilases. In the invasive merozoite, the putative mature protease (p47) is concentrated in dense granules, which are secretory organelles located toward the apical end of the merozoite. At some point following merozoite release and completion of erythrocyte invasion, p47 is secreted from the parasite in a truncated, soluble form. The subcellular location and timing of secretion of p47 suggest that it is likely to play a role in erythrocyte invasion. PfSUB-1 is a new potential target for antimalarial drug development.