TY - JOUR
AU - Karmi, Ola
AU - Marjault, Henri-Baptiste
AU - Pesce, Luca
AU - Carloni, Paolo
AU - Onuchic, Jose’ N.
AU - Jennings, Patricia A.
AU - Mittler, Ron
AU - Nechushtai, Rachel
TI - The unique fold and lability of the [2Fe-2S] clusters of NEET proteins mediate their key functions in health and disease
JO - Journal of biological inorganic chemistry
VL - 23
IS - 4
SN - 1432-1327
CY - Berlin
PB - Springer
M1 - FZJ-2018-01344
SP - 599-612
PY - 2018
AB - 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
LB - PUB:(DE-HGF)16
C6 - pmid:29435647
UR - <Go to ISI:>//WOS:000435600800012
DO - DOI:10.1007/s00775-018-1538-8
UR - https://juser.fz-juelich.de/record/843804
ER -