A single malaria merozoite serine protease mediates shedding of multiple surface proteins by juxtamembrane cleavage
A single malaria merozoite serine protease mediates shedding of multiple surface proteins by juxtamembrane cleavage
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DOI：
10.1074/jbc.m302160200
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发表时间：
2003-06-27
影响因子：
4.8
通讯作者：
Blackman, MJ
中科院分区：
文献类型：
--
作者：
Howell, SA;Wells, I;Blackman, MJ
疟疾蛋白酶的红细胞侵袭伴随着被调节的分泌细胞器的调节，称为微分。恶性疟原虫顶端膜抗原-1（PFAMA-1）在入侵中起着必不可少的作用，从微生物转移到寄生虫表面上，并且在入侵期间以可溶性形式脱离蛋白水解。我们先前在不完全的质谱图数据的基础上提出了PFAMA-1脱落是由于两个替代位置的裂解而导致的。现在，我们最终证明，PFAMA-1胞外域仅是由于单个位点的裂解而从Merozoite中脱离的，距离预测的跨膜跨膜序列仅29个残基。值得注意的是，这种裂解是由膜结合的寄生虫丝氨酸蛋白酶介导的，与负责脱落的Merozoite表面蛋白-1（MSP-1）复合物是一种丰富的，丰富的糖基磷脂酰磷脂酰糖醇锚定的多蛋白复合蛋白。 MSP-1的处理对于入侵至关重要。我们的结果表明，具有广泛的底物特异性的多功能丝氨酸SHEDDASE的Merozoite表面上存在。我们进一步证明，PFAMA-1的易位和脱落是肌动蛋白依赖性过程。
Erythrocyte invasion by the malaria merozoite is accompanied by the regulated discharge of apically located secretory organelles called micronemes. Plasmodium falciparum apical membrane antigen-1 ( PfAMA-1), which plays an indispensable role in invasion, translocates from micronemes onto the parasite surface and is proteolytically shed in a soluble form during invasion. We have previously proposed, on the basis of incomplete mass spectrometric mapping data, that PfAMA-1 shedding results from cleavage at two alternative positions. We now show conclusively that the PfAMA-1 ectodomain is shed from the merozoite solely as a result of cleavage at a single site, just 29 residues away from the predicted transmembrane-spanning sequence. Remarkably, this cleavage is mediated by the same membrane-bound parasite serine protease as that responsible for shedding of the merozoite surface protein-1 (MSP-1) complex, an abundant, glycosylphosphatidylinositol-anchored multiprotein complex. Processing of MSP-1 is essential for invasion. Our results indicate the presence on the merozoite surface of a multifunctional serine sheddase with a broad substrate specificity. We further demonstrate that translocation and shedding of PfAMA-1 is an actinin-dependent process.