The Plasmodium falciparum apicoplast cysteine desulfurase provides sulfur for both iron-sulfur cluster assembly and tRNA modification.
The Plasmodium falciparum apicoplast cysteine desulfurase provides sulfur for both iron-sulfur cluster assembly and tRNA modification.
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恶性疟原虫apicoplast半胱氨酸脱硫酶为铁硫簇组装和tRNA修饰提供硫。
DOI：
10.7554/elife.84491
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发表时间：
2023-05-11
期刊：
影响因子：
7.7
通讯作者：
Prigge ST
中科院分区：
文献类型：
--
作者：
Swift RP;Elahi R;Rajaram K;Liu HB;Prigge ST
铁硫簇（FeS）是一种古老而普遍存在的蛋白质辅因子，在细胞生物学的许多方面发挥着重要作用。这些辅因子不能在细胞内被清除或运输，因此必须在需要它们的任何亚细胞区室中合成。我们研究了FeS合成蛋白中发现的残留质体细胞器，称为顶质体，人类疟疾寄生虫恶性疟原虫。使用化学旁路方法，我们删除了四个参与硫获取和簇组装的FeS途径蛋白，并证明它们都是寄生虫生存所必需的。然而，这些缺失对顶质体细胞器的影响不同。缺失的半胱氨酸脱硫酶SufS导致破坏的顶质体细胞器和细胞器基因组的损失，而其他的删除不影响细胞器的维护。最终，我们发现SufS对细胞器维护的需求不是由其在FeS生物合成中的作用驱动的，而是由其在生成硫以供MnmA使用的功能驱动的，MnmA是一种我们定位于顶质体的tRNA修饰酶。MnmA和SufS活性与细菌MnmA及其同源半胱氨酸脱硫酶的互补强烈表明寄生虫SufS为顶质体中的FeS生物合成和tRNA修饰提供硫。寄生虫SufS的双重作用很可能在其他含质体的生物中发现，并突出了这种酶在质体生物学中的核心作用。
Iron-sulfur clusters (FeS) are ancient and ubiquitous protein cofactors that play fundamental roles in many aspects of cell biology. These cofactors cannot be scavenged or trafficked within a cell and thus must be synthesized in any subcellular compartment where they are required. We examined the FeS synthesis proteins found in the relict plastid organelle, called the apicoplast, of the human malaria parasite Plasmodium falciparum. Using a chemical bypass method, we deleted four of the FeS pathway proteins involved in sulfur acquisition and cluster assembly and demonstrated that they are all essential for parasite survival. However, the effect that these deletions had on the apicoplast organelle differed. Deletion of the cysteine desulfurase SufS led to disruption of the apicoplast organelle and loss of the organellar genome, whereas the other deletions did not affect organelle maintenance. Ultimately, we discovered that the requirement of SufS for organelle maintenance is not driven by its role in FeS biosynthesis, but rather, by its function in generating sulfur for use by MnmA, a tRNA modifying enzyme that we localized to the apicoplast. Complementation of MnmA and SufS activity with a bacterial MnmA and its cognate cysteine desulfurase strongly suggests that the parasite SufS provides sulfur for both FeS biosynthesis and tRNA modification in the apicoplast. The dual role of parasite SufS is likely to be found in other plastid-containing organisms and highlights the central role of this enzyme in plastid biology.
影响因子：
4.6
作者：
Tewari SG;Kwan B;Elahi R;Rajaram K;Reifman J;Prigge ST;Vaidya AB;Wallqvist A
通讯作者：
Wallqvist A
影响因子：
6.4
作者：
Swift RP;Rajaram K;Elahi R;Liu HB;Prigge ST
通讯作者：
Prigge ST