Probing the activities of the Ccm proteins of the cytochrome c biosynthesis system

蛋白质是复杂的生物分子，对所有活细胞的结构和功能都是必不可少的。为了使它们的功能多样化，蛋白质使用被称为辅因子的额外分子，其中有许多类型。血红素就是这样一种辅因子；它是一种中心带有铁原子的有机化合物，在不同的细胞过程中具有许多基本功能。许多含有血红素的蛋白质在细胞内形成键后会经历一个过程；这些蛋白质被称为细胞色素c，在呼吸作用和涉及电子转移的反应中是必不可少的。事实上，细胞色素c被认为是进化过程中出现的最早的蛋白质类别之一。在其他情况下，血红素与蛋白质结合，但不与蛋白质形成键，例如在血红蛋白中，它使用血红素来结合血液中的氧气。在血红素辅因子与细胞色素结合的情况下，需要其他蛋白质来协助这一反应，这不是自发的。以典型的实验室细菌E.Coli为模型系统，我们研究了这一复杂且涉及大量蛋白质的血红素附着过程。出乎意料的是，人们发现这些系统在不同类型的细胞中是不同的。我们提出的研究试图利用各种实验方法和技术来了解这些蛋白质是如何发挥作用的。一旦我们阐明了细菌中血红素与细胞色素结合的细胞机制，我们就有可能设计针对这些蛋白质的药物。这是可能的，因为人类存在一个完全不同的系统，将血红素附着到我们的细胞色素上，例如，允许我们有选择地针对致病细菌。为了完成对构成生命的基本生化反应的描述，理解细胞色素c的制造过程作为基本的和中心的生物过程也是很重要的。

Proteins are complex biomolecules that are essential to the structure and function of all living cells. In order to diversify their functions, proteins use additional molecules called cofactors, of which there are many types. Heme is one such cofactor; it is an organic chemical with an iron atom in the centre and has many essential functions in different cellular processes. Many proteins that contain heme undergo a process after they are made in the cell in which bonds are formed between the protein and the heme; these are called cytochromes c and are essential in respiration and in reactions that involve the transfer of electrons. In fact, cytochromes c are believed to be one of the earliest classes of protein to have appeared in evolution. In other cases, heme associates with proteins without forming bonds with them, for example in hemoglobin, which uses the heme to bind oxygen in blood. In the case where the heme cofactor becomes bonded to the cytochrome, other proteins are needed to assist in this reaction, which is not spontaneous. Using the prototypical laboratory bacterium E. coli as a model system, we study this process of heme attachment, which is complex and involves a large number of proteins. Unexpectedly, it has been found that these systems differ in different types of cells. Our proposed research seeks to understand how these proteins function, using a variety of experimental approaches and techniques. Once we have elucidated the cellular mechanisms of attaching heme to cytochromes in bacteria, we might have the possibility of designing drugs to target these proteins. This would be possible because a completely different system exists in humans to attach heme to our cytochromes, allowing us to selectively target disease-causing bacteria, for example. It is also important to understand the process of making cytochromes c as a fundamental and central biological process, in order to complete a description of the essential biochemical reactions that constitute life.