3ree | pdb_00003ree
Crystal structure of mitoNEET
Structural highlights
Publication Abstract from PubMedBinding of the thiazolidinedione antidiabetic drug pioglitazone led to the discovery of a novel outer mitochondrial membrane protein of unknown function called mitoNEET. The protein is homodimeric and contains a uniquely ligated two iron-two sulfur cluster in each of its two cytosolic domains. Electrospray ionization mass spectrometry was employed to characterize solutions of the soluble cytosolic domain (amino acids 32-108) of the protein. Ions characteristic of dimers containing the cofactors were readily detected under native conditions. mitoNEET responded to exposure to solutions at low pH by dissociation to give monomers that retained the cofactor, followed by dissociation of the cofactor in a concerted fashion. mitoNEET formed complexes with resveratrol-3-sulfate, one of the primary metabolites of the natural product resveratrol. Resveratrol itself showed no tendency to interact with mitoNEET. The formation of complexes was evident in both electrospray ionization mass spectrometry and isothermal titration calorimetry measurements. Up to eight molecules of the compound associated with the dimeric form of the protein in a sequential fashion. Dissociation constants determined by micorcalorimetry were in the range 5-16 muM for the various binding sites. The only other known naturally ocurring binding partner for mitoNEET at present is NADPH. It is very interesting that the iron-sulfur cluster containing protein interacts with two potentially redox active substances at the surface of mitochondria. These findings provide a new direction for research into two poorly understood, yet biomedically relevant species. Complexes of the Outer Mitochondrial Membrane Protein mitoNEET with Resveratrol-3-sulfate.,Arif W, Xu S, Isailovic D, Geldenhuys WJ, Carroll RT, Funk MO Biochemistry. 2011 May 17. PMID:21591687[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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