Laboratories and faculty

Structural Life Science

Outline of Research and Education

In the cells, various proteins are involved in a variety of fundamental biological phenomena, especially motions. To understand life, it is crucial to know how these proteins function in the cell. Unfortunately, molecular mechanisms of most of these proteins are still unclear. To unveil such mechanisms, our laboratory is working on various proteins. In particular, we are focusing on how proteins, small molecules, and ions are transported across membranes and how newly-synthesized proteins are folded into their functional states. This transportation and protein biogenesis are mediated by dedicated proteins including chaperones, proteases, transporters, channels, and translocases (Fig. 1, 2). Some of these membrane proteins can be drug targets. Also, there are proteins which drive the motility of the cell itself. Cilia and flagella are such organelles which are composed of over 600 kinds of proteins. To understand how these proteins work, it is crucial to know their detailed structures. Thus, our laboratory conducts fundamental research by structural biological analyses in combination with other newly developed methods.

The first step of our typical strategy is to elucidate the protein structure at the atomic and amino acid levels (Fig. 3). By obtaining detailed structural information of target proteins, much more insights into how these proteins function can be provided. This is the greatest advantage of uncovering the details of protein structure. The next step is to reveal proposed molecular mechanisms based on protein’s structural information by performing functional analyses. Recently, we are also attempting to visualize protein dynamics by single-molecule analyses. By utilizing several different methods for our research, our results provide new concepts that will change the contents of the textbooks.

Major Research Topics

  1. Transportation across cell membranes and protein biogenesis.
  2. Molecular function and dynamics of proteins
  3. X-ray crystallography and cryo-electron microscopy
Fig. 1
Fig. 1 Conserved protein translocation across the membrane via translocon.
Fig. 2
Fig. 2 Membrane transporters
Fig. 3
Fig. 3  Outline of our research

References

  1. Shahrizal M. et al., J. Mol. Biol. 431, 625-635, 2019
  2. Haruyama T. et al., Structure 27, 152-160, 2019
  3. Furukawa A. et al., Structure 26, 485-489, 2018
  4. Ichikawa M. et al., Nat. Commun., 8, 15035, 2017
  5. Tanaka Y., Iwaki S., and Tsukazaki T. Structure 25, 1455-1460, 2017
  6. Furukawa A. et al., Cell Rep., 19, 895-901, 2017
  7. Tanaka Y. et al., Cell Rep., 13, 1561-1568, 2015
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  9. Tanaka Y. et al., Nature, 496, 247-251, 2013
  10. Tsukazaki T. et al., Nature, 474, 235-238, 2011
  11. Tsukazaki T. et al., Nature, 455, 988-911, 2008