Protein Structural Information Analysis Team



「タンパク質立体構造に指南された創薬戦略（SGDD : Structure Guided Drug Development）」を実現するには、その基礎となるタンパク質立体構造の解析が必要です。

そこで、当チームでは、特に膜タンパク質に有効と考えられる電子顕微鏡による構造解析と、 複合体などの高分解能構造を得るのに重要なＸ線結晶構造解析を行い、その基盤技術開発を進めています。







膜タンパク質は脂質二重層の中にあり、そのため、膜タンパク質の生体内に近い状態での高分解能な構造を決定するには、 脂質二重層中に膜タンパク質が規則正しく並んだ二次元結晶からの電子線結晶構造解析が適していると考えられます。
そこで、その基盤技術の開発と実際の膜蛋白質への応用を行っています。
また、複合体の解析に適した単粒子解析技術の改良も行っています。

2011

Redox and metal-regulated oligomeric state for human porphobilinogen synthase activation. Amino Acids. in press. Sawada, N., Nagahara, N., Arisaka, F., Mitsuoka, K., and Minami, M.

Obtaining high-resolution images of biological macromolecules by using a cryo-electron microscope with a liquid-helium cooled stage. Micron. 42, 100-106. Mitsuoka, K.

Mitsugumin 23 forms a massive bowl-shaped assembly and cation-conducting channel. Biochemistry. 50, 2623-2632. Venturi E, Mio K, Nishi M, Ogura T, Moriya T, Pitt SJ, Okuda K, Kakizawa S, Sitsapesan R, Sato C, Takeshima H.

Mitsugumin 23 forms a massive bowl-shaped assembly and cation-conducting channel. J Biol Chem. 286, 1999-2007. Murai T, Maruyama Y, Mio K, Nishiyama H, Suga M, Sato C.

2010

Single particle reconstruction of membrane proteins: a tool for understanding the 3D structure of disease-related macromolecules. Prog. Biophys. Mol. Biol. 103, 122-130. Mio, K., Maruyama, Y., Ogura, T., Kawata, M., Moriya, T., Mio, M., and Sato, C.

Sequential assembly of the wedge of the baseplate of phage T4 in the presence and absence of gp11 as monitored by analytical ultracentrifugation. Macromol. Biosci. 10, 808-813. Yap, M. L., Mio, K., Ali, S., Minton, A., Kanamaru, S., and Arisaka, F.

Atmospheric scanning electron microscope observes cells and tissues in open medium through silicon nitride film. J. Struct. Biol. 169, 438-449. Nishiyama, H,, Suga, M., Ogura, T., Maruyama, Y., Koizumi, M., Mio, K., Kitamura, S., and Sato, C.

Helical image reconstruction of the outward-open human erythrocyte band 3 membrane domain in tubular crystals. J. Struct. Biol. 169, 406-412. Yamaguchi, T., Fujii, T., Abe, Y., Hirai, T., Kang, D., Namba, K., Hamasaki, N., and Mitsuoka, K.

Keap1 is a forked-stem dimer structure with two large spheres enclosing the intervening, double glycine repeat, and C-terminal domains. Proc. Natl. Acad. Sci. USA. 107, 2842-2847. Ogura, T., Tong, K. I., Mio, K., Maruyama, Y., Kurokawa, H., Sato, C., and Yamamoto, M.

The baseplate wedges of bacteriophage T4 spontaneously assemble into hubless baseplate-like structure in vitro. J. Mol. Biol. 395, 349-360. Yap, M. L., Mio, K., Leiman, P. G., Kanamaru, S., and Arisaka, F.

The C-terminal coiled-coil of the bacterial voltage-gated sodium channel NaChBac is not essential for tetramer formation, but stabilizes subunit-to-subunit interactions. Prog Biophys Mol Biol. 103, 111-121. Mio K, Mio M, Arisaka F, Sato M, Sato C.

2009

Cryo-EM structure of the native GroEL-GroES complex from thermus thermophilus encapsulating substrate inside the cavity. Structure. 17, 287-293. Kanno, R., Koike-Takeshita, A., Yokoyama, K., Taguchi, H., Mitsuoka, K.

2008

Structural basis for induced formation of the inflammatory mediator prostaglandin E2. Proc. Natl. Acad. Sci. USA. 105, 11110-11115. Jegerschöld, C., Pawelzik, S. C., Purhonen, P., Bhakat, P., Gheorghe, K. R., Gyobu, N., Mitsuoka, K., Morgenstern, R., Jakobsson, P. J., Hebert, H.

Neuromyelitis optica and anti-aquaporin-4 antibodies measured by an enzyme-linked immunosorbent assay. J Neuroimmunol. 196, 181-187. Hayakawa, S., Mori, M., Okuta, A., Kamegawa, A., Fujiyoshi, Y., Yoshiyama, Y., Mitsuoka, K., Ishibashi, K., Sasaki, S., Hattori, T., Kuwabara, S.

2007

Dodecamer rotor ring defines H+/ATP ratio for ATP synthesis of prokaryotic V-ATPase from Thermus thermophilus. Proc. Natl. Acad. Sci. USA. 104, 20256-20261. Toei, M., Gerle, C., Nakano, M., Tani, K., Gyobu, N., Tamakoshi, M., Sone, N., Yoshida, M., Fujiyoshi, Y., Mitsuoka, K., Yokoyama, K.

Simulation of charge effects on density maps obtained by high-resolution electron crystallography. J. Electron Microsc. 56, 131-140. Hirai, T., Mitsuoka, K., Kidera, A., Fujiyoshi, Y.

Aquaporin-11 containing a divergent NPA motif has normal water channel activity. Biochim. Biophys. Acta. 1768, 688-693. Yakata, K., Hiroaki, Y., Ishibashi, K., Sohara, E., Sasaki, S., Mitsuoka, K., Fujiyoshi, Y.

2006

Structural basis for detoxification and oxidative stress protection in membranes. J. Mol. Biol. 360, 934-945. Holm, P. J., Bhakat, P., Jegerschold, C., Gyobu, N., Mitsuoka, K., Fujiyoshi, Y., Morgenstern, R., Hebert, H.

Two-dimensional Crystallization and Analysis of Projection Images of Intact Thermus thermophilus VATPase. J. Struct. Biol. 153, 200-206. Gerle, C., Tani, K., Yokoyama, K., Tamakoshi, M., Yoshida, M., Fujiyoshi, Y. and Mitsuoka, K.

Implications of the Aquaporin-4 Structure on Array Formation and Cell Adhesion. J. Mol. Biol. 355, 628-639. Hiroaki, Y., Tani, K., Kamegawa, A., Gyobu, N., Nishikawa, K., Suzuki, H., Walz, T., Sasaki, S., Mitsuoka, K., Kimura, K., Mizoguchi, A. and Fujiyoshi, Y.

2005

Electron tomography reveals diverse conformations of integrin αIIbβ3 in the active state. J Struct Biol. 150, 259-267. Iwasaki, K., Mitsuoka, K., Fujiyoshi, Y., Fujisawa, Y., Kikuchi, M., Sekiguchi, K., and Yamada, T.

2004

Improved specimen preparation for cryo-electron microscopy using a symmetric carbon sandwich technique. J Struct Biol. 146, 325-333. Gyobu, N., Tani, K., Hiroaki, Y., Kamegawa, A., Mitsuoka, K., Fujiyoshi, Y.