A03-2：Molecular Mechanism for Signal Transduction in Dynamics of Biometals
Koichiro Ishimori
（Department of Chemistry, Faculty of Science, Hokkaido University）
Lab website/ Twitter
Iron is the most “abundant” trace metal element in vivo, which plays central roles in various kinds of essential biological processes including respiratory, energy generation, and cellular metabolisms. Iron deficient, therefore, results in serious dysfunction of iron-containing proteins required for these essential biological processes, while excess amounts of iron in cells also severely damage to the cellular components by the generation of reactive oxygen species (ROS). To maintain the cellular iron homeostasis, living organisms have developed elegant and sophisticated regulation systems. We have focused on molecular regulations to maintain the cellular iron homeostasis and tried to elucidate the molecular mechanisms to induce functional defects due to impaired iron metabolisms. In this Scientific Research on Innovative Areas, based on the functional and structural characterization of proteins regulating the cellular iron homeostasis and detailed analysis of interactions among these proteins, we will elucidate molecular regulation mechanisms for dynamics of cellular iron mediated by heme as the signaling molecule and to establish the research basis of “Biometal Science”. Also, to discuss cellular dynamics and functional analysis of toxic metals, we will follow cellular responses to “perturbation” in the regulation mechanism for dynamics of iron in cells by using biochemical and cell biological analysis, which also provides further insights into mechanisms to convert an essential metal, iron, to a toxic metal.
Major publications
Y. Nishitani, H. Okutani, Y. Takeda, T. Uchida, K. Iwai, and *K. Ishimori
“Specific Heme Binding to Heme Regulatory Motifs in Iron Regulatory Proteins and Its Functional Significance”
Journal of Inorganic Biochemistry, 2019, 198, in press
doi: 10.1016/j.jinorgbio.2019.110726
M. Ogura, R. Endo, H. Ishikawa, Y. Takeda, T. Uchida, K. Iwai, K. Kobayashi, and *K. Ishimori
“Redox-dependent Axial Ligand Replacement and Its Functional Significance in Heme-bound Iron Regulatory Proteins”
Journal of Inorganic Biochemistry, 2018, 182, 238-248
doi: 10.1016/j.jinorgbio.2018.01.007
*K. Kobayashi, M. Nakagaki, H. Ishikawa, K. Iwai, M. R. O’Brian, and K. Ishimori
“Redox-Dependent Dynamics in Heme-Bound Bacterial Iron Response Regulator (Irr) Protein”
Biochemistry, 2016, 55, 4047–4054
doi: 10.1021/acs.biochem.6b00512
*Y. Kabe, T. Nakane, I. Koike, T. Yamamoto, Y. Sugiura, E. Harada, K. Sugase, T. Shimamura, M. Ohmura, K. Muraoka, A. Yamamoto, T. Uchida, S. Iwata, Y. Yamaguchi, E. Krayukhina, M. Noda, H. Handa, K. Ishimori, S. Uchiyama, *T. Kobayashi, and *M. Suematsu
“Haem-dependent Dimerization of PGRMC1/Sigma-2 Receptor Facilitates Cancer Proliferation and Chemoresistance”
Nature Communication, 2016, 7, 11030
doi: 10.1038/ncomms11030
C. Kitatsuji, K. Izumi, S. Nambu, M. Kurogochi, T. Uchida, S. Nishimura, K. Iwai, M. R. O’Brian, M. Ikeda-Saito, and *K. Ishimori
“Protein Oxidation Mediated by Heme-induced Active Site Conversion Specific for Heme-regulated Transcription Factor, Iron Response Regulator”
Scientific Reports, 2016, 6, 18703
doi: 10.1038/srep18703