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人类线粒体铁氧化还原蛋白1（FDX1）和铁氧化还原蛋白2（FDX2）均与半胱氨酸脱硫酶结合，并为铁硫簇生物合成提供电子。

Human Mitochondrial Ferredoxin 1 (FDX1) and Ferredoxin 2 (FDX2) Both Bind Cysteine Desulfurase and Donate Electrons for Iron-Sulfur Cluster Biosynthesis.

作者信息

Cai Kai, Tonelli Marco, Frederick Ronnie O, Markley John L

机构信息

Mitochondrial Protein Partnership, Center for Eukaryotic Structural Genomics, and ‡National Magnetic Resonance Facility at Madison, Biochemistry Department, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States.

出版信息

Biochemistry. 2017 Jan 24;56(3):487-499. doi: 10.1021/acs.biochem.6b00447. Epub 2017 Jan 11.

DOI:10.1021/acs.biochem.6b00447
PMID:28001042
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5267338/
Abstract

Ferredoxins play an important role as an electron donor in iron-sulfur (Fe-S) cluster biosynthesis. Two ferredoxins, human mitochondrial ferredoxin 1 (FDX1) and human mitochondrial ferredoxin 2 (FDX2), are present in the matrix of human mitochondria. Conflicting results have been reported regarding their respective function in mitochondrial iron-sulfur cluster biogenesis. We report here biophysical studies of the interaction of these two ferredoxins with other proteins involved in mitochondrial iron-sulfur cluster assembly. Results from nuclear magnetic resonance spectroscopy show that both FDX1 and FDX2 (in both their reduced and oxidized states) interact with the protein complex responsible for cluster assembly, which contains cysteine desulfurase (NFS1), ISD11 (also known as LYRM4), and acyl carrier protein (Acp). In all cases, ferredoxin residues close to the Fe-S cluster are involved in the interaction with this complex. Isothermal titration calorimetry results showed that FDX2 binds more tightly to the cysteine desulfurase complex than FDX1 does. The reduced form of each ferredoxin became oxidized in the presence of the cysteine desulfurase complex when l-cysteine was added, leading to its conversion to l-alanine and the generation of sulfide. In an in vitro reaction, the reduced form of each ferredoxin was found to support Fe-S cluster assembly on ISCU; the rate of cluster assembly was faster with FDX2 than with FDX1. Taken together, these results show that both FDX1 and FDX2 can function in Fe-S cluster assembly in vitro.

摘要

铁氧化还原蛋白在铁硫（Fe-S）簇生物合成中作为电子供体发挥着重要作用。两种铁氧化还原蛋白，即人类线粒体铁氧化还原蛋白1（FDX1）和人类线粒体铁氧化还原蛋白2（FDX2），存在于人类线粒体基质中。关于它们在线粒体铁硫簇生物发生中的各自功能，已有相互矛盾的报道。我们在此报告了对这两种铁氧化还原蛋白与参与线粒体铁硫簇组装的其他蛋白质相互作用的生物物理研究。核磁共振光谱结果表明，FDX1和FDX2（无论其还原态还是氧化态）均与负责簇组装的蛋白质复合物相互作用，该复合物包含半胱氨酸脱硫酶（NFS1）、ISD11（也称为LYRM4）和酰基载体蛋白（Acp）。在所有情况下，靠近Fe-S簇的铁氧化还原蛋白残基都参与了与该复合物的相互作用。等温滴定量热法结果表明，FDX2比FDX1更紧密地结合半胱氨酸脱硫酶复合物。当添加L-半胱氨酸时，每种铁氧化还原蛋白的还原形式在半胱氨酸脱硫酶复合物存在下被氧化，导致其转化为L-丙氨酸并产生硫化物。在体外反应中，发现每种铁氧化还原蛋白的还原形式都支持ISCU上的Fe-S簇组装；FDX2的簇组装速率比FDX1快。综上所述，这些结果表明FDX1和FDX2在体外的Fe-S簇组装中均能发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e28/5267338/07c2790ba0ef/bi-2016-00447x_0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e28/5267338/8f8d87243c67/bi-2016-00447x_0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e28/5267338/e2032832f806/bi-2016-00447x_0005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e28/5267338/760cfa14b4fa/bi-2016-00447x_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e28/5267338/cc0a8e987996/bi-2016-00447x_0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e28/5267338/07c2790ba0ef/bi-2016-00447x_0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e28/5267338/8f8d87243c67/bi-2016-00447x_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e28/5267338/c7863d721468/bi-2016-00447x_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e28/5267338/3118ea1c4097/bi-2016-00447x_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e28/5267338/45b5df0c903f/bi-2016-00447x_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e28/5267338/fe589ee7c48c/bi-2016-00447x_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e28/5267338/e2032832f806/bi-2016-00447x_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e28/5267338/a5cec1b77468/bi-2016-00447x_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e28/5267338/760cfa14b4fa/bi-2016-00447x_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e28/5267338/cc0a8e987996/bi-2016-00447x_0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e28/5267338/07c2790ba0ef/bi-2016-00447x_0010.jpg

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