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

了解组装必需的铁硫簇辅助因子的分子机器

• 批准号: 2869102
• 金额: --
• 依托单位: University of East Anglia
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2869102
• 关键词: Understanding; molecular; machine; assembles; essential

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.

铁硫（FES）簇是蛋白质的无机辅因子，它们在所有类型的细胞中都广泛分布，它们在电子转移，催化和作为传感器中的作用，在多个必需过程中，例如呼吸，光合作用和核酸代谢。它们不会在细胞中自发形成，因此必须组装。这必须以受调节的方式发生，因为铁和硫虽然对生命必不可少，但也具有本质上的毒性。因此，自然已经进化出了高度复杂且受到严格调节的分子机器，用于FES生物发生，这些机器在整个生命的王国中都在进化上保守，并且在过去〜20年中发现了所有这些机器的重要性。这些机器对人类生命的重要性被越来越多地与越来越多的疾病联系在一起，这些疾病似乎与铁蛋白蛋白质及其形成型相关。当这些机器的任何部分分解时，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，但是还有很多要学习的知识。理解簇形成所涉及的步骤受到缺乏有关中间人的确切序列和性质的详细信息的限制，这些信息是形成的，它们形成了相互作用以及如何调节Thie的整体过程。 UEA的Le Brun Lab最近表明，天然条件下的质谱法对于FES簇蛋白的研究非常有用。该蛋白质生物化学项目将利用包括天然质谱在内的一系列技术，为细菌FES簇生物发生的步骤提供新的见解。