MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone.

Abstract	Iron-sulfur (Fe-S) proteins are key players in vital processes involving energy homeostasis and metabolism from the simplest to most complex organisms. We report a 1.5 A x-ray crystal structure of the first identified outer mitochondrial membrane Fe-S protein, mitoNEET. Two protomers intertwine to form a unique dimeric structure that constitutes a new fold to not only the approximately 650 reported Fe-S protein structures but also to all known proteins. We name this motif the NEET fold. The protomers form a two-domain structure: a beta-cap domain and a cluster-binding domain that coordinates two acid-labile 2Fe-2S clusters. Binding of pioglitazone, an insulin-sensitizing thiazolidinedione used in the treatment of type 2 diabetes, stabilizes the protein against 2Fe-2S cluster release. The biophysical properties of mitoNEET suggest that it may participate in a redox-sensitive signaling and/or in Fe-S cluster transfer.
Authors	Mark L Paddock, Sandra E Wiley, Herbert L Axelrod, Aina E Cohen, Melinda Roy, Edward C Abresch, Dominique Capraro, Anne N Murphy, Rachel Nechushtai, Jack E Dixon, Patricia A Jennings
Journal	Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 104 Issue 36 Pg. 14342-7 (Sep 04 2007) ISSN: 0027-8424 [Print] United States
PMID	17766440 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References	CISD1 protein, human Iron-Binding Proteins Iron-Sulfur Proteins Membrane Proteins Mitochondrial Proteins Thiazolidinediones Pioglitazone
Topics	Crystallography, X-Ray Humans Iron-Binding Proteins (chemistry, genetics, metabolism) Iron-Sulfur Proteins (chemistry, genetics, metabolism) Membrane Proteins (chemistry, genetics, metabolism) Mitochondrial Membranes (metabolism) Mitochondrial Proteins (chemistry, genetics, metabolism) Models, Molecular Pioglitazone Protein Binding Protein Folding Protein Structure, Quaternary Protein Structure, Tertiary Thiazolidinediones (chemistry)

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