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[Fe–S] biogenesis and unusual assembly of the ISC scaffold complex in the Plasmodium falciparum mitochondrion
Molecular Microbiology ( IF 3.6 ) Pub Date : 2021-05-25 , DOI: 10.1111/mmi.14735
Mohammad Sadik 1 , Mohammad Afsar 1 , Ravishankar Ramachandran 1 , Saman Habib 1
Affiliation  

The malaria parasite harbors two [Fe–S] biogenesis pathways of prokaryotic origin–the SUF and ISC systems in the apicoplast and mitochondrion, respectively. While the SUF machinery has been delineated, there is little experimental evidence on the ISC pathway. We confirmed mitochondrial targeting of Plasmodium falciparum ISC proteins followed by analyses of cysteine desulfurase, scaffold, and [Fe–S]-carrier components. PfIscU functioned as the scaffold in complex with the PfIscS–PfIsd11 cysteine desulfurase and could directly assemble [4Fe–4S] without prior [2Fe–2S] formation seen in other homologs. Small angle X-ray scattering and spectral studies showed that PfIscU, a trimer, bound one [4Fe–4S]. In a deviation from reported complexes from other organisms, the P. falciparum desulfurase-scaffold complex assembled around a PfIscS tetramer instead of a dimer, resulting in a symmetric hetero-hexamer [2× (2PfIscS–2PfIsd11–2PfIscU)]. PfIscU directly transferred [4Fe–4S] to the apo-protein aconitase B thus abrogating the requirement of intermediary proteins for conversion of [2Fe–2S] to [4Fe–4S] before transfer to [4Fe–4S]-recipients. Among the putative cluster-carriers, PfIscA2 was more efficient than PfNifU-like protein; PfIscA1 primarily bound iron, suggesting its potential role as a Fe2+ carrier/donor. Our results identify the core P. falciparum ISC machinery and reveal unique features compared with those in bacteria or yeast and human mitochondria.

中文翻译:

[Fe-S] 恶性疟原​​虫线粒体中 ISC 支架复合物的生物发生和异常组装

疟疾寄生虫具有两种原核来源的 [Fe-S] 生物发生途径——分别位于顶质体和线粒体中的 SUF 和 ISC 系统。虽然已经描述了 SUF 机制,但关于 ISC 途径的实验证据很少。我们证实了恶性疟原虫ISC 蛋白的线粒体靶向,然后分析了半胱氨酸脱硫酶、支架和 [Fe-S]-载体成分。Pf IscU 作为与Pf IscS- Pf Isd11 半胱氨酸脱硫酶复合的支架,可以直接组装 [4Fe-4S],而无需在其他同源物中形成 [2Fe-2S]。小角 X 射线散射和光谱研究表明PfIscU 是一种三聚体,结合了一个 [4Fe-4S]。在从来自其它生物体的报道复合物的偏离,该恶性疟原虫desulfurase的支架组装复杂围绕Pf的ISCS的四聚体,而不是一个二聚物,从而产生对称的杂六聚体[2×(2 Pf的ISCS-2 Pf的Isd11-2 Pf的IscU)]。Pf IscU 直接将 [4Fe-4S] 转移到脱辅基蛋白乌头酸酶 B,从而消除了在转移到 [4Fe-4S] 受体之前将 [2Fe-2S] 转化为 [4Fe-4S] 对中间蛋白的要求。在假定的簇载体中,Pf IscA2 比Pf NifU 样蛋白更有效;IscA1 主要结合铁,表明其作为 Fe 2+载体/供体的潜在作用。我们的结果确定了核心恶性疟原虫ISC 机制,并揭示了与细菌或酵母和人类线粒体相比的独特特征。
更新日期:2021-05-25
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