Tangled web of interactions among proteins involved in iron-sulfur cluster assembly as unraveled by NMR, SAXS, chemical crosslinking, and functional studies.

Tangled web of interactions among proteins involved in iron-sulfur cluster assembly as unraveled by NMR, SAXS, chemical crosslinking, and functional studies.
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DOI:
10.1016/j.bbamcr.2014.11.020
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发表时间:
2015-06
影响因子:
5.1
通讯作者:
Markley, John L.
Markley, John L.
中科院分区:
生物学2区
文献类型:
--
作者:
Kim, Jin Hae;Bothe, Jameson R.;Alderson, T. Reid;Markley, John L.

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含有铁硫(Fe-S)簇的蛋白质在进化的早期就出现了,对生命至关重要。生物体已经进化出由专门的蛋白质组成的机器,这些蛋白质一起有效地组装Fe-S簇,以最大限度地减少细胞暴露于其有毒成分:铁和硫化物离子。迄今为止,研究得最好的系统是大肠杆菌的铁硫簇(isc)操纵子及其编码的八种ISC蛋白。在过去的五年中,我们的研究已经确定了支架蛋白(IscU)的两种功能构象状态,并表明与IscU相互作用的其他ISC蛋白更喜欢结合一种构象状态或其他构象状态。从分析的NMR光谱衍生网络的相互作用ISC蛋白质和小角X射线散射(SAXS),化学交联实验,和功能测定,我们已经构建了工作模型的Fe-S簇组装和交付。未来的工作需要验证和完善已经了解到的关于E。大肠杆菌系统,并将这些发现扩展到酵母和人类线粒体的同源Fe-S簇生物合成机制。本文是特刊的一部分,题为:Fe/S蛋白质:分析,结构,功能,生物起源和疾病。
Proteins containing iron–sulfur (Fe–S) clusters arose early in evolution and are essential to life. Organisms have evolved machinery consisting of specialized proteins that operate together to assemble Fe–S clusters efficiently so as to minimize cellular exposure to their toxic constituents: iron and sulfide ions. To date, the best studied system is the iron sulfur cluster (isc) operon of Escherichia coli, and the eight ISC proteins it encodes. Our investigations over the past five years have identified two functional conformational states for the scaffold protein (IscU) and have shown that the other ISC proteins that interact with IscU prefer to bind one conformational state or the other. From analyses of the NMR spectroscopy-derived network of interactions of ISC proteins and small-angle X-ray scattering (SAXS), chemical crosslinking experiments, and functional assays, we have constructed working models for Fe–S cluster assembly and delivery. Future work is needed to validate and refine what has been learned about the E. coli system and to extend these findings to the homologous Fe–S cluster biosynthetic machinery of yeast and human mitochondria. This article is part of a Special Issue entitled: Fe/S proteins: Analysis, structure, function, biogenesis and diseases.
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期刊: BIOCHEMISTRY
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