The unique fold and lability of the [2Fe-2S] clusters of NEET proteins mediate their key functions in health and disease.
The unique fold and lability of the [2Fe-2S] clusters of NEET proteins mediate their key functions in health and disease.
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DOI：
10.1007/s00775-018-1538-8
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Nechushtai R
中科院分区：
文献类型：
--
作者：
Karmi O;Marjault HB;Pesce L;Carloni P;Onuchic JN;Jennings PA;Mittler R;Nechushtai R
NEET蛋白包括一类新的[2Fe-2S]簇蛋白。在人类中，三个基因编码NEET蛋白：cisd1编码mitoNEET（mNT），cisd2编码营养剥夺自噬因子-1（NAF-1），cisd3编码MiNT（Miner2）。这些最近发现的蛋白质在与正常代谢和疾病相关的许多过程中起着关键作用。事实上，NEET蛋白参与细胞中的铁、Fe-S和活性氧稳态，并在调节细胞凋亡和自噬中发挥重要作用。mNT和NAF-1是同源二聚体，位于线粒体外膜上。NAF-1还存在于ER相关线粒体膜（MAM）和ER的膜中。MiNT是一种在簇周围的分子表面具有明显不对称性的单体。与其旁系同源物mNT和NAF-1不同，它存在于线粒体内。NAF-1和mNT与植物同源二聚体NEET蛋白（At-NEET）共享相似的骨架折叠，而MiNT的骨架折叠类似于细菌MiNT蛋白。尽管这些蛋白质的氨基酸组成的变化，所有NEET蛋白保留其独特的CDGSH结构域窝藏其独特的3Cys：1His [2Fe-2S]簇协调通过进化。暴露的配位His显示出将不稳定性传递给NEET蛋白的[2Fe-2S]簇。在这篇小综述中，我们讨论了NEET折叠及其结构元素。特别注意的是独特的不稳定性NEET '[2Fe-2S]簇和暗示后者的NEET蛋白的细胞和系统功能的健康和疾病。
NEET proteins comprise a new class of [2Fe-2S] cluster proteins. In human, three genes encode for NEET proteins: cisd1 encodes mitoNEET (mNT), cisd2 encodes the Nutrient-deprivation autophagy factor-1 (NAF-1) and cisd3 encodes MiNT (Miner2). These recently discovered proteins play key roles in many processes related to normal metabolism and disease. Indeed, NEET proteins are involved in iron, Fe-S, and reactive oxygen homeostasis in cells and play an important role in regulating apoptosis and autophagy. mNT and NAF-1 are homodimeric and reside on the outer mitochondrial membrane. NAF-1 also resides in the membranes of the ER associated mitochondrial membranes (MAM) and the ER. MiNT is a monomer with distinct asymmetry in the molecular surfaces surrounding the clusters. Unlike its paralogs mNT and NAF-1, it resides within the mitochondria. NAF-1 and mNT share similar backbone folds to the plant homodimeric NEET protein (At-NEET), while MiNT’s backbone fold resembles a bacterial MiNT protein. Despite the variation of amino acid composition among these proteins, all NEET proteins retained their unique CDGSH domain harboring their unique 3Cys:1His [2Fe-2S] cluster coordination through evolution. The coordinating exposed His was shown to convey the lability to the NEET proteins’ [2Fe-2S] clusters. In this minireview, we discuss the NEET fold and its structural elements. Special attention is given to the unique lability of the NEETs’ [2Fe-2S] cluster and the implication of the latter to the NEET proteins’ cellular and systemic function in health and disease.
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影响因子：
15
作者：
Bergner M;Dechert S;Demeshko S;Kupper C;Mayer JM;Meyer F
通讯作者：
Meyer F
影响因子：
3.5
作者：
Chang, Natasha C.;Mai Nguyen;Shore, Gordon C.
通讯作者：
Shore, Gordon C.
影响因子：
10.5
作者：
Chen, Yi-Fan;Kao, Cheng-Heng;Tsai, Ting-Fen
通讯作者：
Tsai, Ting-Fen
DOI：
10.1073/pnas.1116369109
发表时间：
2012-02-07
影响因子：
11.1
作者：
Baxter, Elizabeth Leigh;Jennings, Patricia A.;Onuchic, Jose N.
通讯作者：
Onuchic, Jose N.
影响因子：
14.9
作者：
The UniProt Consortium
通讯作者：
The UniProt Consortium