Abstract:
Iron‑sulfur (Fe-S) clusters, inorganic cofactors composed of iron and sulfide, participate in numerous essential redox, non-redox, structural, and regulatory biological processes within the cell. Though structurally and functionally diverse, the list of all proteins in an organism capable of binding one or more Fe-S clusters is referred to as its Fe-S proteome. Importantly, the Fe-S proteome is highly dynamic, with continuous cluster synthesis and delivery by complex Fe-S cluster biogenesis pathways. This cluster delivery is balanced out by processes that can result in loss of Fe-S cluster binding, such as redox state changes, iron availability, and oxygen sensitivity. Despite continued expansion of the Fe-S protein catalogue, it remains a challenge to reliably identify novel Fe-S proteins. As such, high-throughput techniques that can report on native Fe-S cluster binding are required to both identify new Fe-S proteins, as well as characterize the in vivo dynamics of Fe-S cluster binding. Due to the recent rapid growth in mass spectrometry, proteomics, and chemical biology, there has been a host of techniques developed that are applicable to the study of native Fe-S proteins. This review will detail both the current understanding of the Fe-S proteome and Fe-S cluster biology as well as describing state-of-the-art proteomic strategies for the study of Fe-S clusters within the context of a native proteome.
摘要:
铁硫(FeS)簇,由铁和硫化物组成的无机辅因子,参与许多必需的氧化还原,非氧化还原,结构,和调节细胞内的生物过程。尽管结构和功能不同,生物体中能够结合一个或多个FeS簇的所有蛋白质的列表被称为其FeS蛋白质组。重要的是,FeS蛋白质组是高度动态的,通过复杂的FeS簇生物发生途径进行连续簇合成和递送。此集群交付由可能导致FeS集群绑定丢失的进程平衡,如氧化还原状态的变化,铁的可用性,和氧气敏感性。尽管FeS蛋白目录继续扩大,可靠地鉴定新型FeS蛋白仍然是一个挑战。因此,需要能够报告天然FeS簇结合的高通量技术来鉴定新的FeS蛋白,以及表征FeS簇结合的体内动力学。由于质谱最近的快速增长,蛋白质组学,和化学生物学,已经开发了许多适用于天然FeS蛋白研究的技术。这篇综述将详细介绍目前对FeS蛋白质组和FeS簇生物学的理解,以及描述在天然蛋白质组背景下研究FeS簇的最新蛋白质组策略。