Abstract's Details

MitoNEET is a Uniquely Folded 2Fe–2S Outer Mitochondrial Membrane Protein Stabilized by Pioglitazone
Abstract ID	BIO-13
Presenter	Herbert Axelrod
Presentation Type	Poster
Full Author List	H. L. Axelrod (1), A. E. Cohen (1), M. L. Paddock (2), S. E. Wiley (3), M. Roy (4), E. C. Abresch (2), D. Capraro (4), A. N. Murphy (3), R. Nechushtai (6), J. E. Dixon (3,4,5)
Affiliations	(1) Stanford Synchrotron Radiation Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025 (2) Department of Physics, University of California at San Diego, La Jolla, CA 92093 (3) Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093 (4) Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093 (5) Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093 (6) Department of Plant and Environmental Sciences, The Wolfson Centre for Applied Structural Biology, Hebrew University of Jerusalem, Givat Ram 91904, Israel
Category	Bio/Life Sciences
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 Å 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 ~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 b-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.
Footnotes	additional author: P.A. Jennings, 4
Funding Acknowledgement