A pivotal heme-transfer reaction intermediate in cytochrome c biogenesis.
A pivotal heme-transfer reaction intermediate in cytochrome c biogenesis.
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DOI：
10.1074/jbc.m111.313692
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发表时间：
2012-01-20
期刊：
影响因子：
--
通讯作者：
Allen JW
中科院分区：
文献类型：
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作者：
Mavridou DA;Stevens JM;Mönkemeyer L;Daltrop O;di Gleria K;Kessler BM;Ferguson SJ;Allen JW
背景：血红素与细胞色素c的结合是一种催化的翻译后修饰。结果如下：我们确定了一个三元复合物的细胞色素c生物合成蛋白CcmE，血红素，和细胞色素，并证明其功能的意义。结论：该配合物是血红素从细胞色素生物合成器向细胞色素转移的催化中间体。意义：对血红素蛋白生物合成的深入了解。C型细胞色素是广泛分布的蛋白质，是大多数细胞中呼吸或光合作用的基础。它们含有以高度保守、高度立体特异性的翻译后修饰共价结合到蛋白质的血红素。在许多细菌、线粒体和古细菌中，这种血红素附着是由细胞色素c成熟（Ccm）蛋白催化的。在这里，我们确定和表征的血红素伴侣CcmE，血红素和细胞色素c之间的共价，三元复合物。从holo-CcmE复合物的形成发生在体内和体外，并涉及CcmE和脱辅基细胞色素c的特定血红素结合残基。这种复合物的量的增强和减弱与其他Ccm蛋白基因突变的已知后果完全相关。我们提出的复杂的是一个被困的催化中间体在细胞色素c的生物合成过程中，在点的血红素转移从CcmE的细胞色素，在成熟途径的关键步骤。
Background: Heme attachment to cytochrome c is a catalyzed post-translational modification. Results: We identify a ternary complex of the cytochrome c biogenesis protein CcmE, heme, and a cytochrome, and demonstrate its functional significance. Conclusion: The complex is a trapped catalytic intermediate at the point of heme transfer from the cytochrome biogenesis apparatus to the cytochrome. Significance: An insight into biosynthesis of heme proteins. c-Type cytochromes are widespread proteins, fundamental for respiration or photosynthesis in most cells. They contain heme covalently bound to protein in a highly conserved, highly stereospecific post-translational modification. In many bacteria, mitochondria, and archaea this heme attachment is catalyzed by the cytochrome c maturation (Ccm) proteins. Here we identify and characterize a covalent, ternary complex between the heme chaperone CcmE, heme, and cytochrome c. Formation of the complex from holo-CcmE occurs in vivo and in vitro and involves the specific heme-binding residues of both CcmE and apocytochrome c. The enhancement and attenuation of the amounts of this complex correlates completely with known consequences of mutations in genes for other Ccm proteins. We propose the complex is a trapped catalytic intermediate in the cytochrome c biogenesis process, at the point of heme transfer from CcmE to the cytochrome, the key step in the maturation pathway.