Identification of cryptic subunits from an apicomplexan ATP synthase.
Identification of cryptic subunits from an apicomplexan ATP synthase.
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DOI：
10.7554/elife.38097
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发表时间：
2018-09-11
期刊：
影响因子：
7.7
通讯作者：
Lourido S
中科院分区：
文献类型：
--
作者：
Huet D;Rajendran E;van Dooren GG;Lourido S
线粒体ATP合成酶是一种利用质子梯度产生ATP的大分子马达。正确的ATP合酶功能需要一个连接复合物催化和旋转部分的定子。然而，基于序列的搜索未能识别编码顶复门寄生虫（如弓形虫）或引起疟疾的相关生物体中定子亚基的基因。在这里，我们确定了11个以前未知的亚基从弓形虫ATP合酶，缺乏同源物的门外。建模表明，其中两个，ICAP2和ICAP18，是远亲哺乳动物定子亚基。我们的分析表明，这两种蛋白质形成的ATP合成酶复合物的一部分。消耗ICAP2导致异常的线粒体形态，减少耗氧量，和解体的复杂，其作为一个重要组成部分的弓形虫ATP合酶的作用一致。我们的研究结果突出了中央代谢机制的apicomplexans，这可能会揭示新的治疗机会不同的功能。
The mitochondrial ATP synthase is a macromolecular motor that uses the proton gradient to generate ATP. Proper ATP synthase function requires a stator linking the catalytic and rotary portions of the complex. However, sequence-based searches fail to identify genes encoding stator subunits in apicomplexan parasites like Toxoplasma gondii or the related organisms that cause malaria. Here, we identify 11 previously unknown subunits from the Toxoplasma ATP synthase, which lack homologs outside the phylum. Modeling suggests that two of them, ICAP2 and ICAP18, are distantly related to mammalian stator subunits. Our analysis shows that both proteins form part of the ATP synthase complex. Depletion of ICAP2 leads to aberrant mitochondrial morphology, decreased oxygen consumption, and disassembly of the complex, consistent with its role as an essential component of the Toxoplasma ATP synthase. Our findings highlight divergent features of the central metabolic machinery in apicomplexans, which may reveal new therapeutic opportunities.