Crystallographic studies of human MitoNEET.
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.
Hou
Xiaowei
X
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.
Liu
Rujuan
R
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.
Ross
Stuart
S
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.
Smart
Eric J
EJ
Kentucky Pediatric Research Institute, Department of Pediatrics, College of Medicine, University of Kentucky, Lexington, Kentucky 40536-0509.
Zhu
Haining
H
Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, 40536-0509. Electronic address: haining@uky.edu.
Gong
Weimin
W
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.
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
C525595:CISD1 protein, human; D033862:Iron-Binding Proteins; D007506:Iron-Sulfur Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D006639:Histidine