title: Crystallographic studies of human MitoNEET.
abstract: MitoNEET was identified as an outer mitochondrial membrane protein that can potentially bind the anti-diabetes drug pioglitazone. The crystal structure of the cytoplasmic mitoNEET (residues 33-108) is determined in this study. The structure presents a novel protein fold and contains a [2Fe-2S] cluster-binding domain. The [2Fe-2S] cluster is coordinated to the protein by Cys-72, Cys-74, Cys-83, and His-87 residues. This coordination is also novel compared with the traditional [2Fe-2S] cluster coordinated by four cysteines or two cysteines and two histidines. The cytoplasmic mitoNEET forms homodimers in solution and in crystal. The dimerization is mainly mediated by hydrophobic interactions as well as hydrogen bonds coordinated by two water molecules binding at the interface. His-87 residue, which plays an important role in the coordination of the [2Fe-2S] cluster, is exposed to the solvent on the dimer surface. It is proposed that mitoNEET dimer may interact with other proteins via the surface residues in close proximity to the [2Fe-2S] cluster.
authors: National Key Laboratory of Macrobiomolecule, Center for Structural and Molecular Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P. R. China; School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China.
authors: Xiaowei
authors: X
authors: Hou
authors: National Key Laboratory of Macrobiomolecule, Center for Structural and Molecular Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P. R. China; School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China; Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, 40536-0509.
authors: Rujuan
authors: R
authors: Liu
authors: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, 40536-0509; Kentucky Pediatric Research Institute, Department of Pediatrics, College of Medicine, University of Kentucky, Lexington, Kentucky 40536-0509.
authors: Stuart
authors: S
authors: Ross
authors: Kentucky Pediatric Research Institute, Department of Pediatrics, College of Medicine, University of Kentucky, Lexington, Kentucky 40536-0509.
authors: Eric J
authors: EJ
authors: Smart
authors: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, 40536-0509. Electronic address: haining@uky.edu.
authors: Haining
authors: H
authors: Zhu
authors: National Key Laboratory of Macrobiomolecule, Center for Structural and Molecular Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P. R. China; School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China. Electronic address: wgong@ibp.ac.cn.
authors: Weimin
authors: W
authors: Gong
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray / Q000379:methods*; D003593:Cytoplasm / Q000378:metabolism; D019281:Dimerization; D006639:Histidine / Q000737:chemistry; D006801:Humans; D033862:Iron-Binding Proteins / Q000737:chemistry*; D007506:Iron-Sulfur Proteins / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry*; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: C525595:CISD1 protein, human; D033862:Iron-Binding Proteins; D007506:Iron-Sulfur Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D006639:Histidine