Journal
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
Volume 23, Issue 4, Pages 599-612Publisher
SPRINGER
DOI: 10.1007/s00775-018-1538-8
Keywords
[2Fe-2S]; Iron-sulfur clusters; Cisdq(1-3) encoded NEET proteins; NEET-fold; NEET-cluster lability
Funding
- BSF [2015831]
- NIH [GM101467]
- Human Brain Project
- [NSF-MCB-1613462]
- [NSF-PHY-1427654]
- [NSF-CHE-1614101]
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1614101] Funding Source: National Science Foundation
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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. [GRAPHICS] .
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