Laboratories and faculty

Structural Life Science

Outline of Research and Education

In the cells, various biomolecules, including proteins, RNAs, and DNAs, are involved in various fundamental biological phenomena. Therefore, it is crucial to know how these biomolecules function in the cell to understand life. Unfortunately, the molecular mechanisms of most of these proteins are still unclear. To unveil such mechanisms, our laboratory is working on elucidating biomolecule functions. In particular, we focus 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 sophisticated proteins, including chaperones, proteases, transporters, channels, and translocases (Figs. 1, 2). Some of these membrane proteins can be drug targets. It is crucial to know their detailed structures to understand how these proteins work. Thus, our laboratory conducts fundamental research through structural biological analyses combined 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 insight into how these proteins can function. Getting high-resolution structures is the most significant 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 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
  4. PiXie (pulse-chase and in vivo photo-cross-linking experiment)
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. Miyazaki et al., eLife, 10, e7054 2021
  2. Tanaka et al., Sci. Adv., 6, eaba7637, 2020
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  5. Furukawa A. et al., Structure 26, 485-489, 2018
  6. Tanaka Y., Iwaki S., and Tsukazaki T. Structure 25, 1455-1460, 2017
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  8. Tanaka Y. et al., Cell Rep., 13, 1561-1568, 2015
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  10. Tanaka Y. et al., Nature, 496, 247-251, 2013
  11. Tsukazaki T. et al., Nature, 474, 235-238, 2011
  12. Tsukazaki T. et al., Nature, 455, 988-911, 2008