Acidification of the Malaria Parasite's Digestive Vacuole by a H+-ATPase and a H+-pyrophosphatase*
Acidification of the Malaria Parasite's Digestive Vacuole by a H+-ATPase and a H+-pyrophosphatase*
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H -ATP 酶和 H -焦磷酸酶* 酸化疟疾寄生虫的消化液泡*
DOI：
10.1074/jbc.m208648200
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
K. Kirk
中科院分区：
文献类型：
--
作者：
K. Saliba;R. J. Allen;Stephanie Zissis;P. Bray;S. Ward;K. Kirk
当它在人体红细胞内生长时，疟原虫（Plasmodium falciparum）摄取红细胞胞质溶胶，通过内吞进食机制将其沉积在“消化泡”（一种专门的酸性细胞器）中。消化空泡是血红蛋白降解的场所，是疟原虫色素（一种有毒血红素的惰性生物晶体）的储存场所，是许多抗疟药物的作用场所，也是已知参与抗疟药物耐药性的蛋白质的场所。该细胞器的酸性pH值被认为在其各种功能中发挥着关键作用;然而，维持液泡内pH值的机制尚不清楚。在这项研究中，我们已经使用了技术的组合，以证明两个离散的H+泵送机制，都能够酸化液泡内部的恶性疟原虫消化空泡膜上的存在。一个是V型H+-ATP酶，对康卡霉素A和巴弗洛霉素A1敏感。另一个是H+-焦磷酸酶，它被NaF抑制，并表现出对K+的部分依赖性。的H+-焦磷酸酶的操作是依赖于镁2 +-焦磷酸盐复合物的存在下，和动力学实验得到的结果与作为蛋白质的抑制剂的游离焦磷酸盐一致。在恶性疟原虫消化泡上存在的H+-ATP酶和H+-焦磷酸酶的组合与植物细胞酸性液泡中的情况相似。
As it grows within the human erythrocyte, the malaria parasite, Plasmodium falciparum, ingests the erythrocyte cytosol, depositing it via an endocytotic feeding mechanism in the “digestive vacuole,” a specialized acidic organelle. The digestive vacuole is the site of hemoglobin degradation, the storage site for hemozoin (an inert biocrystal of toxic heme), the site of action of many antimalarial drugs, and the site of proteins known to be involved in antimalarial drug resistance. The acidic pH of this organelle is thought to play a critical role in its various functions; however, the mechanisms by which the pH within the vacuole is maintained are not well understood. In this study, we have used a combination of techniques to demonstrate the presence on the P. falciparum digestive vacuole membrane of two discrete H+ pumping mechanisms, both capable of acidifying the vacuole interior. One is a V-type H+-ATPase, sensitive to concanamycin A and bafilomycin A1. The other is a H+-pyrophosphatase, which was inhibited by NaF and showed a partial dependence on K+. The operation of the H+-pyrophosphatase was dependent on the presence of a Mg2+-pyrophosphate complex, and kinetic experiments gave results consistent with free pyrophosphate acting as an inhibitor of the protein. The presence of the combination of a H+-ATPase and a H+-pyrophosphatase on the P. falciparumdigestive vacuole is similar to the situation in the acidic tonoplasts (vacuoles) of plant cells.
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影响因子：
1.5
作者：
McIntosh, MT;Drozdowicz, YM;Vaidya, AB
通讯作者：
Vaidya, AB
影响因子：
16
作者：
Fidock, DA;Nomura, T;Wellems, TE
通讯作者：
Wellems, TE
DOI：
10.1073/pnas.87.8.2931
发表时间：
1990-04-01
影响因子：
11.1
作者：
GOLDBERG, DE;SLATER, AFG;HENDERSON, GB
通讯作者：
HENDERSON, GB
DOI：
10.1016/s0035-9203(97)90110-3
发表时间：
1997-05-01
影响因子：
2.2
作者：
Cranmer, SL;Magowan, C;Cooke, BM
通讯作者：
Cooke, BM