The Heme a Synthase Cox15 Associates with Cytochrome c Oxidase Assembly Intermediates during Cox1 Maturation

The Heme a Synthase Cox15 Associates with Cytochrome c Oxidase Assembly Intermediates during Cox1 Maturation
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DOI:
10.1128/mcb.00747-13
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发表时间:
2013-10-01
影响因子:
5.3
通讯作者:
Rehling, Peter
Rehling, Peter
中科院分区:
生物学2区
文献类型:
--
作者:
Bareth, Bettina;Dennerlein, Sven;Rehling, Peter

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Cox1是细胞色素c氧化酶的核心亚基,在13个亚基酶复合物的组装过程中接受两个血红素a辅因子。然而,在组装过程的哪一步以及血红素如何插入到Cox1中仍然是一个谜。酵母SURF1同源物Shy1与血红素向Cox1的转移有关,而血红素a合成酶Cox15则催化血红素a合成的最后一步。在这里,我们对含有Shy1的细胞色素c氧化酶组装中间体进行了全面的分析。我们的分析表明,Cox15在细胞色素c氧化酶组装中发挥作用,这是独立于其作为血红素a合成酶的功能的。Cox15与Shy1形成蛋白复合物,并与独立于Shy1功能的含cox1复合物结合。这些发现表明,Shy1不是作为血红素a合成酶和成熟的Cox1之间的移动血红素载体,而是与Cox15合作,在细胞色素c氧化酶的早期组装中间体中进行血红素转移和插入。
Cox1, the core subunit of the cytochrome c oxidase, receives two heme a cofactors during assembly of the 13-subunit enzyme complex. However, at which step of the assembly process and how heme is inserted into Cox1 have remained an enigma. Shy1, the yeast SURF1 homolog, has been implicated in heme transfer to Cox1, whereas the heme a synthase, Cox15, catalyzes the final step of heme a synthesis. Here we performed a comprehensive analysis of cytochrome c oxidase assembly intermediates containing Shy1. Our analyses suggest that Cox15 displays a role in cytochrome c oxidase assembly, which is independent of its functions as the heme a synthase. Cox15 forms protein complexes with Shy1 and also associates with Cox1-containing complexes independently of Shy1 function. These findings indicate that Shy1 does not serve as a mobile heme carrier between the heme a synthase and maturing Cox1 but rather cooperates with Cox15 for heme transfer and insertion in early assembly intermediates of cytochrome c oxidase.