Richard-Fogal Cynthia L, Frawley Elaine R, Bonner Eric R, Zhu Huifen, San Francisco Brian, Kranz Robert G
Department of Biology, Washington University, St Louis, MO 63130, USA.
EMBO J. 2009 Aug 19;28(16):2349-59. doi: 10.1038/emboj.2009.189. Epub 2009 Jul 23.
A pathway for cytochrome c maturation (Ccm) in bacteria, archaea and eukaryotes (mitochondria) requires the genes encoding eight membrane proteins (CcmABCDEFGH). The CcmABCDE proteins are proposed to traffic haem to the cytochrome c synthetase (CcmF/H) for covalent attachment to cytochrome c by unknown mechanisms. For the first time, we purify pathway complexes with trapped haem to elucidate the molecular mechanisms of haem binding, trafficking and redox control. We discovered an early step in trafficking that involves oxidation of haem (to Fe(3+)), yet the final attachment requires reduced haem (Fe(2+)). Surprisingly, CcmF is a cytochrome b with a haem never before realized, and in vitro, CcmF functions as a quinol:haem oxidoreductase. Thus, this ancient pathway has conserved and orchestrated mechanisms for trafficking, storing and reducing haem, which assure its use for cytochrome c synthesis even in limiting haem (iron) environments and reducing haem in oxidizing environments.
细菌、古菌和真核生物（线粒体）中细胞色素c成熟（Ccm）的一条途径需要编码八种膜蛋白（CcmABCDEFGH）的基因。有人提出，CcmABCDE蛋白将血红素转运至细胞色素c合成酶（CcmF/H），通过未知机制将其共价连接到细胞色素c上。我们首次纯化了捕获有血红素的途径复合物，以阐明血红素结合、转运和氧化还原控制的分子机制。我们发现了转运过程中的一个早期步骤，涉及血红素氧化（生成Fe(3+)），但最终连接需要还原型血红素（Fe(2+)）。令人惊讶的是，CcmF是一种含有前所未有的血红素的细胞色素b，在体外，CcmF作为一种喹啉：血红素氧化还原酶发挥作用。因此，这条古老的途径具有保守且精心编排的血红素转运、储存和还原机制，即使在血红素（铁）有限的环境中也能确保其用于细胞色素c的合成，并在氧化环境中还原血红素。
