Mapping cellular Fe-S cluster uptake and exchange reactions - divergent pathways for iron-sulfur cluster delivery to human ferredoxins.
Mapping cellular Fe-S cluster uptake and exchange reactions - divergent pathways for iron-sulfur cluster delivery to human ferredoxins.
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DOI：
10.1039/c6mt00193a
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发表时间：
2016-12-07
期刊：
影响因子：
--
通讯作者：
Cowan JA
中科院分区：
文献类型：
--
作者：
Fidai I;Wachnowsky C;Cowan JA
铁氧还蛋白是生物电子转移反应的蛋白质介质，通常含有[2Fe-2S]或[4Fe-4S]簇。已在人类基因组中鉴定出两种铁氧还蛋白同源物，Fdx 1和Fdx 2，它们在蛋白质序列上具有43%的同一性和69%的相似性，并且都结合[2Fe-2S]簇。尽管高度相似，但两种铁氧化还原蛋白在不同的生理途径中发挥非常特定的作用，并且在功能上不能相互取代。已经报道了真核和原核铁氧化还原蛋白及其同系物从支架/递送蛋白如IscU、伊萨、谷氧还蛋白和Nfu接收其Fe-S簇。然而，铁氧还蛋白接收[2Fe-2S]簇的优选和生理相关途径受到推测，并且没有明确鉴定。在这项工作中，我们报告在体外紫外可见（UV-vis）圆二色性研究[2Fe-2S]集群转移到铁氧化还原蛋白从各种合作伙伴。结果表明，快速和定量转移到铁氧化还原素从几个供体蛋白（IscU，Isa 1，Grx 2和Grx 3）。从Isa 1到Fdx 2的转移也比IscU到Fdx 2的转移快，这表明Fdx 2可以从Isa 1而不是IscU接收其簇。其他几个转移组合也进行了调查，结果表明一个复杂的，但动力学详细的地图细胞簇贩运。这是为线粒体和胞质溶胶中所有可能的铁硫簇转移途径构建网络图的第一步，为最可能的细胞途径和这些途径中可能的冗余提供了见解。[2Fe-2S]簇转移到来自几种供体蛋白的细胞Fdx的映射提出了映射细胞簇运输的方法。
Ferredoxins are protein mediators of biological electron-transfer reactions and typically contain either [2Fe–2S] or [4Fe–4S] clusters. Two ferredoxin homologues have been identified in the human genome, Fdx1 and Fdx2, that share 43% identity and 69% similarity in protein sequence and both bind [2Fe-2S] clusters. Despite the high similarity, the two ferredoxins play very specific roles in distinct physiological pathways and cannot replace each other in function. Both eukaryotic and prokaryotic ferredoxins and homologues have been reported to receive their Fe-S cluster from scaffold/delivery proteins such as IscU, Isa, glutaredoxins, and Nfu. However, the preferred and physiologically relevant pathway for receiving the [2Fe-2S] cluster by ferredoxins is subject to speculation and is not clearly identified. In this work, we report on in vitro UV-visible (UV-vis) circular dichroism studies of [2Fe–2S] cluster transfer to the ferredoxins from a variety of partners. The results reveal rapid and quantitative transfer to both ferredoxins from several donor proteins (IscU, Isa1, Grx2, and Grx3). Transfer from Isa1 to Fdx2 was also observed to be faster than that of IscU to Fdx2, suggesting that Fdx2 could receive its cluster from Isa1 instead of IscU. Several other transfer combinations were also investigated and the results suggest a complex, but kinetically detailed map for cellular cluster trafficking. This is the first step toward building a network map for all of the possible iron-sulfur cluster transfer pathways in the mitochondria and cytosol, providing insights on the most likely cellular pathways and possible redundancies in these pathways. Mapping of [2Fe-2S] cluster transfer to cellular Fdx’s from several donor Proteins suggest an approach to mapping cellular cluster trafficking.
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影响因子：
2.9
作者：
Gao, Huanyao;Subramanian, Sowmya;Johnson, Michael K.
通讯作者：
Johnson, Michael K.
DOI：
10.1111/j.1742-4658.2011.08178.x
发表时间：
2011-07
期刊：
The FEBS journal
影响因子：
--
作者：
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通讯作者：
Hirschi KD
影响因子：
4.8
作者：
Bonomi, F;Iametti, S;Vickery, LE
通讯作者：
Vickery, LE
影响因子：
4.8
作者：
Kumanovics, Attila;Chen, Opal S.;Kaplan, Jerry
通讯作者：
Kaplan, Jerry
DOI：
10.1073/pnas.1114372109
发表时间：
2012-01-10
影响因子：
11.1
作者：
Kim, Jin Hae;Tonelli, Marco;Markley, John L.
通讯作者：
Markley, John L.