Food vacuole plasmepsins are processed at a conserved site by an acidic convertase activity in Plasmodium falciparum
Food vacuole plasmepsins are processed at a conserved site by an acidic convertase activity in Plasmodium falciparum
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DOI：
10.1016/s0166-6851(03)00119-1
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发表时间：
2003-07-01
影响因子：
1.5
通讯作者：
Goldberg, DE
中科院分区：
文献类型：
--
作者：
Banerjee, R;Francis, SE;Goldberg, DE
红细胞内恶性疟原虫。在酸性食物液泡（FV）中消化大量血红蛋白。四种同源的天冬氨酸蛋白酶参与FV内的血红蛋白降解。Plasmepsin (PM) I和II被认为启动天然血红蛋白分子的降解。PM IV和组织天冬氨酸蛋白酶（HAP）在该通路的下游作用于变性珠蛋白。PM I和PM II已被证明是作为酶原合成的，并通过蛋白水解去除propiece而激活。在这项研究中，我们已经确定，FV plasmepins的蛋白水解过程发生在一个保守的Leu-Gly二肽基基之后，具有均匀的动力学、pH和抑制剂敏感性。我们已经开发了一种无细胞的体外处理实验，可以产生正确处理的血浆蛋白酶。我们的数据表明，原质体蛋白酶的加工不是自催化的，而是由一个单独的加工酶介导的。这种转化酶需要酸性条件，并且仅被钙蛋白酶抑制剂阻断，这表明它可能是一种非典型的钙蛋白酶样蛋白酶。(C) 2003 Elsevier Science B.V.版权所有
Intraerythrocytic Plasmodium falciparum. digests vast amounts of hemoglobin within an acidic food vacuole (FV). Four homologous aspartic proteases participate in hemoglobin degradation within the FV. Plasmepsin (PM) I and II are thought to initiate degradation of the native hemoglobin molecule. PM IV and histo-aspartic protease (HAP) act on denatured globin further downstream in the pathway. PM I and II have been shown to be synthesized as zymogens and activated by proteolytic removal of a propiece. In this study, we have determined that the proteolytic processing of FV plasmepsins occurs immediately after a conserved Leu-Gly dipeptidyl motif with uniform kinetics and pH and inhibitor sensitivities. We have developed a cell-free in vitro processing assay that generates correctly processed plasmepsins. Our data suggest that proplasmepsin processing is not autocatalytic, but rather is mediated by a separate processing enzyme. This convertase requires acidic conditions and is blocked only by the calpain inhibitors, suggesting that it may be an atypical calpain-like protease. (C) 2003 Elsevier Science B.V. All rights reserved.