The Mammalian Proteins MMS19, MIP18, and ANT2 Are Involved in Cytoplasmic Iron-Sulfur Cluster Protein Assembly
The Mammalian Proteins MMS19, MIP18, and ANT2 Are Involved in Cytoplasmic Iron-Sulfur Cluster Protein Assembly
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DOI：
10.1074/jbc.m112.431270
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发表时间：
2012-12-21
影响因子：
4.8
通讯作者：
Uringa, Evert-Jan
中科院分区：
文献类型：
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作者：
van Wietmarschen, Niek;Moradian, Annie;Uringa, Evert-Jan
铁-硫(Fe-S)簇是蛋白质的重要辅因子，具有广泛的生物学功能。需要一个专门的胞质Fe-S簇组装(CIA)系统才能将Fe-S簇组装成胞质和核蛋白。在这里，我们证明了哺乳动物核苷酸切除修复蛋白同系物MMS19可以同时结合可能的细胞质铁-硫蛋白组装蛋白CIA01和Fe-S蛋白，证实MMS19是中央情报局机制的中心蛋白，使Fe-S簇供体蛋白和接收脱辅基蛋白接近。此外，我们还发现有丝分裂纺锤体相关的MMXD复合体亚基MIP18也能与CIAO_1和Fe-S蛋白相互作用。具体地说，它结合了Fe-S蛋白中的Fe-S簇协调区。此外，我们还发现，腺苷二磷酸/三磷酸腺苷转位酶2(ANT2)与铁-S脱脂蛋白和MMS19在CIA复合体中相互作用，但不与单独的蛋白相互作用。综上所述，这些结果阐明了中情局晚期复合体的组成和相互作用。
Iron-sulfur (Fe-S) clusters are essential cofactors of proteins with a wide range of biological functions. A dedicated cytosolic Fe-S cluster assembly (CIA) system is required to assemble Fe-S clusters into cytosolic and nuclear proteins. Here, we show that the mammalian nucleotide excision repair protein homolog MMS19 can simultaneously bind probable cytosolic iron-sulfur protein assembly protein CIAO1 and Fe-S proteins, confirming that MMS19 is a central protein of the CIA machinery that brings Fe-S cluster donor proteins and the receiving apoproteins into proximity. In addition, we show that mitotic spindle-associated MMXD complex subunit MIP18 also interacts with both CIAO1 and Fe-S proteins. Specifically, it binds the Fe-S cluster coordinating regions in Fe-S proteins. Furthermore, we show that ADP/ATP translocase 2 (ANT2) interacts with Fe-S apoproteins and MMS19 in the CIA complex but not with the individual proteins. Together, these results elucidate the composition and interactions within the late CIA complex.