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Characterization of Arabidopsis NEET reveals an ancient role for NEET proteins in iron metabolism
Authors:Nechushtai Rachel  Conlan Andrea R  Harir Yael  Song Luhua  Yogev Ohad  Eisenberg-Domovich Yael  Livnah Oded  Michaeli Dorit  Rosen Rachel  Ma Vincent  Luo Yuting  Zuris John A  Paddock Mark L  Cabantchik Zvi Ioav  Jennings Patricia A  Mittler Ron
Institution:The Alexander Silberman Institute of Life Science and the Wolfson Center for Applied Structural Biology, Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Abstract:The NEET family is a newly discovered group of proteins involved in a diverse array of biological processes, including autophagy, apoptosis, aging, diabetes, and reactive oxygen homeostasis. They form a novel structure, the NEET fold, in which two protomers intertwine to form a two-domain motif, a cap, and a unique redox-active labile 2Fe-2S cluster binding domain. To accelerate the functional study of NEET proteins, as well as to examine whether they have an evolutionarily conserved role, we identified and characterized a plant NEET protein. Here, we show that the Arabidopsis thaliana At5g51720 protein (At-NEET) displays biochemical, structural, and biophysical characteristics of a NEET protein. Phenotypic characterization of At-NEET revealed a key role for this protein in plant development, senescence, reactive oxygen homeostasis, and Fe metabolism. A role in Fe metabolism was further supported by biochemical and cell biology studies of At-NEET in plant and mammalian cells, as well as mutational analysis of its cluster binding domain. Our findings support the hypothesis that NEET proteins have an ancient role in cells associated with Fe metabolism.
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