A01：Elucidation of the molecular mechanism of pore-forming toxins for Fe acquisition by pathogenic bacterium
Takeshi YOKOYAMA
（Graduate School of Life Sciences, Tohoku University）
Lab website
Pore-forming toxins (PFT) are secreted by pathogens for disrupting erythrocyte in their host by forming pores on the cell membrane. Pathogens producing PFTs utilize this system for efficiently acquiring iron from heme, which is essential for bacterial growth. Therefore, it is important to elucidate the detailed pore forming mechanism of PFT for understanding and measure of infectious diseases. PFT is secreted as a soluble monoer from bacteria. Subsequently, it forms an intermediate complex called prepore on the cell membrane. Eventually, it inserts stem domain to the cell membrane to form a pore. Until now, structures of PET in these three states by x-ray crystallography have been reported. However, to understand the detailed pore forming mechanism structural analyses of intermediate states connecting these steps and dynamic behavior of how PET forms the pore should be uncovered. Thus, we employ the latest structure analysis techniques such as cryo-electron microscopy (cryo-EM) for further elucidation of the erythrocyte disruption mechanism by pathogens.
Major publications
T. Yokoyama, K. Machida, W. Iwasaki, T. Shigeta, M. Nishimoto, M. Takahashi, A. Sakamoto, M. Yonemochi, Y. Harada, H. Shigematsu, M. Shirouzu, H. Tadakuma, H. Imataka, & T. Ito.
“HCV IRES Captures an Actively Translating 80S Ribosome.”
Molecular cell 2019, 74(6), 1205–1214.e8.
doi: 10.1016/j.molcel.2019.04.022
K. Kashiwagi, T. Yokoyama, M. Nishimoto, M. Takahashi, A. Sakamoto, M. Yonemochi, M. Shirouzu, & T. Ito.
“Structural basis for eIF2B inhibition in integrated stress response.”
Science 2019, 364(6439), 495–499.
doi: 10.1126/science.aaw4104
G. Kasuya, T. Nakane, T. Yokoyama, Y. Jia, M. Inoue, K. Watanabe, R. Nakamura, T. Nishizawa, T. Kusakizako, A. Tsutsumi, H. Yanagisawa, N. Dohmae, M. Hattori, H. Ichijo, Z. Yan, M. Kikkawa, M. Shirouzu, R. Ishitani, & O. Nureki.
“Cryo-EM structures of the human volume-regulated anion channel LRRC8.”
Nature structural & molecular biology 2018, 25(9), 797–804.
doi: 10.1038/s41594-018-0109-6
H. Ehara, T. Yokoyama, H. Shigematsu, S. Yokoyama, M. Shirouzu, & S. I. Sekine.
“Structure of the complete elongation complex of RNA polymerase II with basal factors.”
Science 2017, 357(6354), 921–924.
doi: 10.1126/science.aan8552