Laboratories

Membrane Molecular Biology

Prof. Tsukazaki
Associate Professor
Tomoya TSUKAZAKI
Assistant Professor
Yoshiki TANAKA
Labs HP
http://bsw3.naist.jp/tsukazaki/en.html

Outline of Research and Education

In the cell, a variety of membrane protein complexes is involved in the fundamental biological processes. The Sec membrane protein complex embedded in the cytoplasmic membrane in bacteria or the endoplasmic reticulum membrane in eukaryotes is the essential machinery for translocation of newly synthesized proteins across the membrane (Fig.1). In bacteria, the protein transport to the periplasm via a hetero trimeric complex called Sec translocon, composed of SecY, SecE and SecG, is driven by ATP-dependent motor SecA and proton-dependent motor SecDF cooperatively (Fig.2). We have determined crystal structures of all of the Sec factors and performed structure-directed functional studies, which have enabled us to propose conformational changes of Sec proteins during protein translocation. However, the details of the molecular mechanisms remain unclear. Sec structures of other forms and at high resolution are required to fully understand Sec protein translocation processes. In our laboratory, we perform structural biological analysis, including a new technique for visualizing the protein translocation (Fig.3). Our results will lead to understanding of not only the protein transport across the membrane, but also the transport mechanisms of various materials including drugs.

Major Research Topics

  1. Protein transport across cell membranes
  2. Molecular function and dynamics of membrane proteins

References

  1. Furukawa, Yoshikaie et al., Cell Rep., 19, 895-901, 2017
  2. Tanaka, Sugano et al., Cell Rep., 13, 1561-1568, 2015
  3. Kumazaki K., Chiba S., Takemoto M., Furukawa A. et al., Nature, 509, 516-520, 2014
  4. Tanaka Y. et al., Nature, 496, 247-251, 2013
  5. Tsukazaki T. et al., Nature, 474, 235-238, 2011
  6. Higuchi T., Hattori M., Tanaka Y., et al., Proteins, 76, 768-771, 2009
  7. Tsukazaki T. et al., Nature, 455, 988-911, 2008
  8. Hattori M., Tanaka Y. et al., Nature, 448, 1072-1075, 2007
  9. Vassylyev D.G., Mori H., Vassylyeva M.N., Tsukazaki T. et al., J. Mol. Biol, 364, 248-258, 2006
  10. Mori H., Tsukazaki T. et al., J. Biol. Chem. 278, 14257-14264, 2003
Fig.1
Fig.1 Conserved protein translocation across the membrane.
Fig.2
Fig.2 Bacterial Sec machinery. SecYEG complex provides the pore for protein movement that was driven by two motors, SecA and SecDF.
Fig.3
Fig.3 Our strategy for visualizing protein translocation.
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