McNeil Matthew B, Fineran Peter C
Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Biochim Biophys Acta. 2013 May;1827(5):637-47. doi: 10.1016/j.bbabio.2012.09.003. Epub 2012 Sep 14.
Complex II (also known as Succinate dehydrogenase or Succinate-ubiquinone oxidoreductase) is an important respiratory enzyme that participates in both the tricarboxylic acid cycle and electron transport chain. Complex II consists of four subunits including a catalytic flavoprotein (SdhA), an iron-sulphur subunit (SdhB) and two hydrophobic membrane anchors (SdhC and SdhD). Complex II also contains a number of redox cofactors including haem, Fe-S clusters and FAD, which mediate electron transfer from succinate oxidation to the reduction of the mobile electron carrier ubiquinone. The flavin cofactor FAD is an important redox cofactor found in many proteins that participate in oxidation/reduction reactions. FAD is predominantly bound non-covalently to flavoproteins, with only a small percentage of flavoproteins, such as complex II, binding FAD covalently. Aside from a few examples, the mechanisms of flavin attachment have been a relatively unexplored area. This review will discuss the FAD cofactor and the mechanisms used by flavoproteins to covalently bind FAD. Particular focus is placed on the attachment of FAD to complex II with an emphasis on SdhE (a DUF339/SDH5 protein previously termed YgfY), the first protein identified as an assembly factor for FAD attachment to flavoproteins in prokaryotes. The molecular details of SdhE-dependent flavinylation of complex II are discussed and comparisons are made to known cofactor chaperones. Furthermore, an evolutionary hypothesis is proposed to explain the distribution of SdhE homologues in bacterial and eukaryotic species. Mechanisms for regulating SdhE function and how this may be linked to complex II function in different bacterial species are also discussed. This article is part of a Special Issue entitled: Respiratory complex II: Role in cellular physiology and disease.
复合物II（也称为琥珀酸脱氢酶或琥珀酸-泛醌氧化还原酶）是一种重要的呼吸酶，参与三羧酸循环和电子传递链。复合物II由四个亚基组成，包括一个催化黄素蛋白（SdhA）、一个铁硫亚基（SdhB）和两个疏水膜锚定蛋白（SdhC和SdhD）。复合物II还包含许多氧化还原辅因子，包括血红素、铁硫簇和黄素腺嘌呤二核苷酸（FAD），它们介导从琥珀酸氧化到移动电子载体泛醌还原的电子转移。黄素辅因子FAD是许多参与氧化/还原反应的蛋白质中发现的一种重要氧化还原辅因子。FAD主要以非共价方式与黄素蛋白结合，只有一小部分黄素蛋白，如复合物II，以共价方式结合FAD。除了少数例子外，黄素附着机制一直是一个相对未被探索的领域。本综述将讨论FAD辅因子以及黄素蛋白共价结合FAD所使用的机制。特别关注FAD与复合物II的附着，重点是SdhE（一种以前称为YgfY的DUF339/SDH5蛋白），它是原核生物中第一个被鉴定为FAD附着到黄素蛋白的组装因子的蛋白质。讨论了复合物II依赖SdhE的黄素化的分子细节，并与已知的辅因子伴侣进行了比较。此外，还提出了一个进化假说，以解释SdhE同源物在细菌和真核生物物种中的分布。还讨论了调节SdhE功能的机制以及这可能如何与不同细菌物种中的复合物II功能相关联。本文是名为：呼吸复合物II：在细胞生理学和疾病中的作用的特刊的一部分。
