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，广泛分布于各种细胞中，在呼吸、光合作用和核酸代谢等重要过程中起着电子传递、催化和传感的作用。它们不能在细胞中自发形成，因此必须组装。这必须以一种受管制的方式发生，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生物发生的分子机器，这些机器在生命王国中进化上是保守的，并且都是在过去的~20年中发现的。这些机器对人类生命的重要性通过越来越多的疾病来说明，这些疾病越来越多地与铁硫簇蛋白及其形成的损伤有关。当这些机器的任何一个部件坏了，疾病就会发生。我们对FeS在人类和细菌中组装的理解越来越复杂，但仍有许多需要学习的地方。由于缺乏关于事件的精确顺序和中间体的性质、形成的相互作用以及它们如何调节整个过程的详细信息，对簇形成所涉及的步骤的理解受到限制。UEA的Le Brun实验室最近表明，在自然条件下的质谱法对于FeS簇蛋白的研究非常有用。这个蛋白质生物化学项目将利用一系列技术，包括原生质谱，为细菌FeS簇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.