Understanding the molecular machine that assembles essential iron-sulfur cluster cofactors

铁硫（FeS）簇是蛋白质的无机辅因子，广泛分布于所有类型的细胞中，在电子转移、催化以及呼吸、光合作用和核酸代谢等多种基本过程中起传感器作用。它们不是在细胞中自发形成的，因此必须进行组装。这必须以一种有规律的方式进行，因为铁和硫虽然对生命至关重要，但本质上也是有毒的。因此，自然界已经进化出高度复杂和严格调控的FeS生物发生分子机器，这些机器在进化上保守于整个生命王国，并且都是在过去的20年里发现的。越来越多的疾病似乎与铁硫簇蛋白及其形成的损害有关，这说明了这些机器对人类生命的重要性。当这些机器的任何一个部件发生故障时，就会发生疾病。我们对人类和细菌中FeS组装的理解越来越复杂，但仍有很多东西需要学习。由于缺乏关于事件的精确顺序和中间体的性质、相互作用的形成以及它们如何调节整个过程的详细信息，对集群形成所涉及的步骤的理解受到限制。东英吉利大学的勒布伦实验室最近表明，在自然条件下的质谱法对研究FeS簇蛋白非常有用。这个蛋白质生物化学项目将利用一系列技术，包括天然质谱，为细菌FeS集群生物发生的步骤提供新的见解。

Iron-sulfur (FeS) clusters are inorganic cofactors of proteins that are widely distributed in all types of cells where they function in electron transfer, catalysis and as sensors in multiple essential processes such as respiration, photosynthesis and nucleic acid metabolism. They do not form spontaneously in cells and thus must be assembled. This must occur in a regulated way because iron and sulfur, though essential for life, are also intrinsically toxic. Nature has thus evolved highly complex and tightly regulated molecular machines for FeS biogenesis, which are evolutionarily conserved across the kingdoms of life, and all discovered within the past ~20 years.The importance of these machines for human life is illustrated by the number of diseases that increasingly appear to be linked to impairment of iron-sulfur cluster proteins and their formation. When any of the parts of these machines break down, disease occurs. Our understanding of FeS assembly in humans and bacteria is increasingly sophisticated, but there remains much to learn.Understanding the steps involved in formation of clusters is limited by the lack of detailed information on the precise sequence of events and nature of intermediates, which interactions are formed and how they regulate thie overall process. The Le Brun lab at UEA has recently shown that mass spectrometry under native conditions is extremely useful for studies of FeS cluster proteins. This protein biochemistry project will utilise a range of techniques, including native mass spectrometry, to provide new insight into the steps of bacterial FeS cluster biogenesis.