A01-1:Structural and Functional Characterization of Proteins Related to Biometal Dynamics in Cellular System
Yoshitsugu Shiro
(Graduate School of Life Science, University of Hyogo)
Lab website 1 / Lab website 2

For all living system, an iron (Fe) is an essential element, which is responsible for a variety of physiological actions. Fe is utilized as active sites of Fe-binding proteins after absorption, sensing, storage and transport in cells: i.e., the so-called iron-dynamics in biology. The iron-dynamics is controlled by many proteins through protein-protein interactions and dynamic protein conformational changes in a cellular crowding condition. In human, failure and disturbance of the iron-dynamics, both of which are caused by functional and structural disregulation, causes many diseases. On the other hand, pathogens acquire Fe from the heme iron of hemoglobin of the host (human) blood through the iron-dynamics system. Therefore, inhibitors of the pathogenic iron-dynamics system would be candidates of anti-biotic drugs. In our project, we focus on proteins related to the iron dynamics in human and pathogens, and examine their structural and functional dynamics in cellular system by using time-resolved techniques.

Major publications
T. Hino, Y. Matsumoto, S. Nagano, H. Sugimoto, Y. Fukumori, T. Murata, S. Iwata, Y. Shiro
“Structural Basis of Biological N2O Generation by Bacterial Nitric Oxide Reductase”
Science 2010, 330, 1666-1670

E. Terasaka, K. Yamada, P.-H. Wang, K. Hosokawa, R. Yamagiwa, K. Matsumoto, S. Ishii, T. Mori, K. Yagi, H. Sawai, H. Arai, H. Sugimoto, Y. Sugita, Y. Shiro, T. Tosha
“Dynamics of Nitric Oxide Controlled by Protein Complex in Bacterial System”
Proc. Natl. Acad. Sci. USA 2017, 114, 9888-9893
doi: 10.1073/pnas.1621301114

T. Tosha, T. Nomura, T. Nishida, N. Saeki, K. Okubayashi, R. Yamagiwa, M. Sugahara, T. Nakane, K. Yamashita, K. Hirata, G. Ueno, T. Kimura, T. Hisano, K. Muramoto, H. Sawai, H. Takeda, E. Mizohata, A. Yamashita, Y. Kanematsu, Y. Takano, E. Nango, R. Tanaka, O. Nureki, Y. Ikemoto, H. Murakami, S. Owada, K. Tono, M. Yabashi, M. Yamamoto, H. Ago, S. Iwata, H. Sugimoto, Y. Shiro, M. Kubo
“Capturing an Initial Intermediate during Enzymatic Reaction of P450nor using Time-Resolved XFEL Crystallography and Caged-Substrate”
Nat. Commun. 2017, 8, 1585
doi: 10.1038/s41467-017-01702-1

G. S. A. Wright, A. Saeki, T. Hikima, Y. Nishizono, T. Hisano, M. Yamamoto, S. V. Antonyuk, S. S. Hasnain, Y. Shiro, H. Sawai
“Architecture of a Complete Two-Component Signal Transduction System: Oxygen-Sensing Proteins FixL, FixJ, and The FixL-FixJ Complex”
Sci. Signal. 2018, 11, aaq0825
doi: 10.1126/scisignal.aaq0825

M. Ganasen, H. Togashi, H. Takeda, H. Asakura, T. Tosha, K. Yamashita, K. Hirata, Y. Nariai, T. Urano, X. Yuan, I. Hamza, A. G. Mauk, Y. Shiro, H. Sugimoto, H. Sawai
“Structural Basis for Promotion of Duodenal Iron Absorption by Enteric Ferric Reductase with Ascorbate”
Commun. Biol. 2018, 1: 120
doi: 10.1038/s42003-018-0121-8