Laboratory for Protein Conformation Diseases

We investigate molecular basis of neurodegenerative disorders and psychiatric diseases by using a variety of methods including neurobiology, genetics, structural biology and proteomics. Furthermore, we aim to reveal structural basis of prion strains and transmission barriers in yeast prion systems by various biophysical techniques and yeast genetics. We also search for and analyze novel cytoplasmic genetic elements and functional amyloids that play physiological roles in cells.

Research Subjects

• Molecular basis of neuropsychiatric disorders
• Identification and analysis of novel functional amyloid
• Molecular basis of fromation, propagation and transmission barriers of yeast prion strains

Publications

1. Suzuki, G., and Tanaka, M.:
   "Active conversion to the prion state as a molecular switch for cellular adaptation to environmental stress"
   Bioessays, 35, 12-16 (2013).
2. Suzuki, G., Shimazu, N., and Tanaka, M.:
   "A Yeast Prion, Mod 5, Promotes Acquired Drug Resistance and Cell Survival under Environmental Stress"
   Science, 336, 355-359 (2012).
3. Tanaka, M.:
   "Protein misfolding: tracking a toxic polyglutamine epitope"
   Nat. Chem. Biol., 7, 861-862 (2011).
4. Tonoki, A., Kuranaga, E., Ito, N., Nekooki-Machida, Y., Tanaka, M., and Miura, M.:
   "Aging causes distinct characteristics of polyglutamine amyloids in vivo"
   Genes Cells, 16, 557-64 (2011).
5. Foo, C.K., Ohhashi, Y., Kelly, M.J., Tanaka, M., and Weissman, J.S.:
   "Radically different amyloid conformations dictate the seeding specificity of a chimeric Sup35 prion"
   J. Mol. Biol., 408, 1-8 (2011).
6. Ohhashi, Y., Ito, K., Toyama, GH, Weissman, JS., and Tanaka, M.:
   "Differences in prion strain conformations result from non-native interactions in a nucleus"
   Nat. Chem. Biol., 6, 225-230 (2010).
7. Nekooki-Machida, Y., Kurosawa, M., Nukina, N., Ito, K., Oda, T., and Tanaka, M.:
   "Distinct conformations of in vitro and in vivo amyloids of huntingtin-exon1 show different cytotoxicity"
   Proc. Natl. Acad. Sci. U. S. A., 106, 9679-9684 (2009).
8. Krzewska, J., Tanaka, M., Burston, S.G., and Melki, R.:
   "Biochemical and functional analysis of the assembly of full-length Sup35p and its prion-forming domain"
   J. Biol. Chem., 282, 1679-1686 (2007).
9. Tanaka, M., Collins, S.R., Toyama, B.H., and Weissman, J.S.:
   "The physical basis of how prion conformations determine strain phenotypes"
   Nature, 442, 585-589 (2006).
10. Tanaka, M., Chien, P., Yonekura, K., and Weissman, J.S.:
    "Mechanism of cross-species prion transmission: an infectious conformation compatible with two highly divergent yeast prion proteins"
    Cell, 121, 49-62 (2005).