Molecular and Chemical Life Science :
Multilevel Biomolecular Structure and Dynamics


Structural Biology

Structural Biology

Cells have evolved elaborate internal mechanisms for controlling the quality of proteins. The Laboratory of Design of Biomolecular Function aims to utilize all the techniques of structural biology, biochemistry, proteomics, and cell biology to thoroughly investigate the systems that promote proper folding of proteins and rapidly degrade defective proteins selectively. It is expected that the achievement of this research will help elucidate molecular level mechanisms of various diseases caused by misfolded proteins accumulating in cells.

Research Overview

We have published the following representative papers concerning the research described above.

  1. Han, Ba Bui, Watanabe, S., Nomura, N., Liu, K., Uemura, T., Inoue, M., Tsutsumi, A., Fujita, H., Kinoshita, K. Kato, Y., Iwata, S., Kikkawa, M., and Inaba, K.* “Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn2+ uptake into the Golgi apparatus” Nature Communications 14, 4770 (2023)
  2. Amagai, Y., Yamada, M., Kowada, T., Watanabe, T., Du, Y., Liu, R., Naramoto, S., Watanabe, S., Kyozuka, J., Anelli, T., Tempio, T., Sitia, R., Mizukami, S. and Inaba, K.* “Zinc homeostasis governed by Golgi-resident ZnT family members regulates ERp44-dependent proteostasis at the ER-Golgi interface. Nature Communications 14, 2683 (2023)
  3. Chen, Z., Watanabe, S., Hashida, H., Inoue, M., Daigaku, Y., Kikkawa, M., and Inaba, K.* “Cryo-EM structures of human SPCA1a reveal the mechanism of Ca2+/Mn2+ transport into the Golgi apparatus; Science Advances 9, eadd9742 (2023)
  4. Zhang, Y., Kobayashi, C., Cai, X., Watanabe, S., Tsutsumi, A., Kikkawa, M., Sugita, Y. and Inaba, K.* “Multiple sub-state structures of SERCA2b reveal conformational overlap at transition steps during the catalytic cycle; Cell Reports 41, 111760 (2022)
  5. Zhang, Y., Watanabe, S., Tsutsumi, A., Kadokura, H., Kikkawa, M. and Inaba, K.* “Cryo-EM analysis provides new mechanistic insight into ATP binding to Ca2+-ATPase SERCA2b” EMBO Journal 40, e108482 (2021)
  6. Zhang. Y., Inoue, M., Tsutsumi, A., Watanabe, S., Nishizawa, T., Nagata, K., Kikkawa, M. and Inaba, K.* “Cryo-EM structures of SERCA2b reveal the mechanism of regulation by the luminal extension tail” Science Advances 6, eabb0147 (2020)
  7. Kadokura, H., Dazai, Y., Fukuda, Y., Hirai, N., Nakamura, O., and Inaba, K. “Observing the nonvectorial yet cotranslational folding of a multidomain protein, LDL receptor, in the ER of mammalian cells” Proc. Natl. Acad. Sci. USA. 117, 16401-16408 (2020)
  8. Okumura, M.*, Noi, K., Kanemura, S., Kinoshita, M., Saio, T., Inoue, Y., Hikima, T., Akiyama, S., Ogura, T.* and Inaba, K.* “Dynamic assembly of protein disulfide isomerase in catalysis of oxidative folding” Nature Chemical Biology 15, 499-509 (2019)
  9. Watanabe S., Amagai Y., Sannino S., Tempio T., Anelli T., Harayama M., Masui S., Sorrentino I., Yamada M., Sitia R*, and Inaba K*. “Zinc regulates ERp44-dependent protein quality control in the early secretory pathway.” Nature Communications, 10, 603 (2019)
  10. Inoue, M., Sakuta, N., Watanabe, S., Zhang, Y., Yoshikaie, K., Tanaka, Y., Ushioda, R., Kato, Y., Takagi, J., Tsukazaki, T., Nagata, K. and Inaba, K.* “Structural basis of sarco/endoplasmic reticulum Ca2+-ATPase 2b regulation via transmembrane helix interplay” Cell Reports, 27, 1221-1230 (2019)
  11. Watanabe, S., Harayama, M., Kanemura, S., Sitia, R. and Inaba, K.* “Structural basis of pH-dependent client binding by ERp44, a key regulator of protein secretion at the ER-Golgi interface” Proc. Natl. Acad. Sci. USA. 114, 3224-3232 (2017)
  12. Maegawa, K., Watanabe, S., Noi, K., Okumura, M., Amagai, Y., Inoue, M., Ushioda, R., Nagata, K., Ogura, T. and Inaba, K.* “The highly dynamic nature of ERdj5 is key to efficient elimination of aberrant protein oligomers through ER-associated degradation” Structure, 25, 846-857(2017)
  13. Arai, K., Takei, T., Okumura, M., Watanabe, S., Amagai, Y., Asahina, Y., Moroder, L., Hojo, H.*, Inaba, K.* and Iwaoka, M.* “Preparation of selenoinsulin as a long-lasting insulin analog” Angewandte Chemie 56, 5522-5526 (2017)
  14. Vavassori, S., Cortini, M., Masui, S. Sannino, S., Anelli, T., Caserta, I. R., Fagioli, C., Fornili, A., Mossuto, M. F., Degano, M, Inaba, K. and Sitia, R.* “A pH-Regulated Quality Control Cycle for Surveillance of Secretory Protein Assembly” Molecular Cell 50, 783-792 (2013)
  15. Hagiwara, M., Maegawa, K., Suzuki, M. †, Ushioda, R., Araki, K., Matsimoto, Y., Hoseki, J., Nagata, K.* and Inaba, K.* “Structural basis of an ERAD pathway mediated by the ER-resident disulfide reductasse ERdj5” Molecular Cell 41, 432-444 (2011)
  16. Inaba, K.*, Masui, S., Iida, H. Vavassori, S., Sitia, R. and Suzuki, M. “Crystal structures of human Ero1α reveal the mechanisms of regulated and targeted oxidation of PDI” EMBO Journal 29, 3330-3343 (2010)
  17. Inaba, K.*, Murakami, S., Nakagawa, A., Iida, H., Kinjo, M., Ito, K. and Suzuki, M. “Dynamic nature of disulfide bond formation catalysts revealed by crystal structures of DsbB” EMBO Journal 28, 779-791 (2009)
  18. Inaba, K.*, Murakami, S., Suzuki, M., Nakagawa, A., Yamashita, E., Okada, K. and Ito, K.* “Crystal structure of the DsbB-DsbA complex reveals a mechanism of disulfide bond generation” Cell 127, 789-801 (2006)
  19. Inaba, K., Takahashi, Y. -H., Ito, K. and Hayashi, S. “Critical role of a thiolate-quinone charge transfer complex and its adduct form in de novo disulfide bond generation by DsbB” Proc. Natl. Acad. Sci. USA. 103, 287-292 (2006)
  20. Inaba, K. and Ito, K. “Paradoxical redox properties of DsbB and DsbA in the protein disulfide-introducing reaction cascade” EMBO Journal 21, 2646-2654 (2002)
URLs http://www.tagen.tohoku.ac.jp/labo/inaba/

Faculty Members

Professor INABA Kenji
  • Understanding protein quality control systems in cells at the level of the molecular structure
  • Comprehensive analysis of the disulfide bond network in the endoplasmic reticulum
Associate Professor OKUMURA Masaki (C)
Understanding the protein quality control system as treatments for neurodegenerative diseases
Assistant Professor WATANABE Satoshi
  • Understanding calcium ion control mechanisms in cells
  • Understanding metalloprotein maturation mechanisms