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1 R., Tanabe, A., Golden, S.-S., Johnson, C.-H., & Kondo, T. Science,,. Nishiwaki, T., Iwasaki, H., Ishiura, M., & Kondo, T. Proc. Natl. Acad. Sci. USA,,. Xu, Y., Mori, T., & Johnson, C.-H.EMBO J.,,. Iwasaki, H., Nishiwaki, T., Kitayama, Y., Nakajima, M., & Kondo, T.Proc. Natl. Acad. Sci. USA,,. Kitayama, Y., Iwasaki, H., Nishiwaki T., & Kondo, T. EMBO J.,,. Pattanayek, R., Wang, J., Mori, T., Xu, Y., Johonson, C.-H., & Egli, M.Mol. Cell,,. Nishiwaki, T., Satomi, Y., Nakajima, M., Lee, C., Kiyohara, R., Kageyama, H., Kitayama, Y., Temamoto, M., Yamaguchi, A., Hijikata, A., Go, M., Iwasaki, H., Takao, T., & Kondo, T. Proc. Natl. Acad. Sci. USA,,. Xu, Y., Mori, T., Pattanayek, R., Pattanayek, S., Egli, M., & Johnson, C.-H.Proc. Natl. Acad. Sci. USA,,. Hayashi, F., Iwase, R., Uzumaki, T., & Ishiura, M. Biochem. Biophys. Res. Commun.,,. Tomita, J., Nakajima, M., Kondo, T., & Iwasaki, H. Science,,. Ito, H., Kageyama, H., Mutsuda, M., Nakajima, M., Oyama, T., & Kondo, T.Nat. Struct. Mol. Biol.,,. Nishiwaki, T., Satomi, Y., Kitayama, Y., Terauchi, K., Kiyohara, R., Takao, T., & Kondo, T.EMBO J.,,. Rust, M.-J., Markson, J.-S., Lane, W.-S., Fisher, D.-S., & O Shea, E.-K.Science,,. Kageyama, H., Kondo, T., & Iwasaki, H. J. Biol. Chem.,,. Kageyama, H., Nishiwaki, T., Nakajima, M., Iwasaki, H., Oyama, T., & Kondo, T.Mol. Cell,,. Akiyama, S., Nohara, A., Ito, K., & Maeda, Y.Mol. Cell,,. Terauchi K., Kitayama, Y., Nishiwaki, T., Miwa, K., Murayama, Y., Oyama, T., & Kondo, T.Proc. Natl. Acad. Sci. USA,,. Murakami, R., Miyake, A., Iwase, R., Hayashi, F., Uzumaki, T., & Ishiura, M.,Genes Cells,,. Phosphorylation of cyanobacterial clock protein KaiC Taeko Ohkawa-Nishiwaki Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikisa-ku, Nagoya, Japan RNA RIG-I RNA RIG-I IFN RNA I IFN RNA RNA Toll like receptor TLR TLR TLR RNA dsrna RNA ssrna IFN RNA retinoic acid inducible gene I RIG- I RIG-I RNA N caspase recruitment domain CARD RNA RNA CARD RIG-I RNA RIG-I RNA RIG-I RIG-I melanoma differentiationassociated gene MDA laboratory of genetics and physiology LGP N CARD RIG-I MDA IFN RNA RIG-I MDA ATP
2 RIG-I RIG-I MDA RIG-I ssrna MDA dsrna RNA RNA ATP CARD IPS- CARD IRF NF-κB CARD IPS- MAVS VISA Cardif TRAF FADD RIP IKK IRF- IRF- NF-κB IFN LGP CARD RIG-I MDA RIG-I C repressor domain RD RD CARD RIG-I LGP C RD MDA C LGP RD MDA RIG-I RIG-I MDA RNA
3 RIG-I MDA RNA RIG-I in vitro RNA MDA polyi C dsrna RNA RIG-I ssrna RIG-I RNA RNA mrna trna rrna RIG-I RNA RIG-I VPg RNA RIG-I MDA RNA dsrna RNA MDA RIG-I RNA in vitro RNA ATPase RNA RIG-I ssrna dsrna ATPase RNA dsrna dsrna dsrna RIG-I RIG-I RNA bp dsrna RIG-I dsrna RIG-I ssrna dsrna RIG-I RNA ssrna dsrna RIG-I dsrna RIG-I dsrna RIG-I dsrna RIG-I RNA
4 RIG-I microrna RNA RIG-I dsrna polyi C RIG-I ATPase polyi C RIG- I RIG-I RNA RIG-I RNA RIG-I RNA kda polyi C kda kda RD C CTD RNA RNA RNA CTD RNA RD CTD NMR CTD β β antiparallel antiparallel β β β β ARab GTPase GDP GTP exchange factor MSS MSS Zn CTD Zn X CTD Hopfner CTD Zn Zn RIG-I Zn RIG-I RNA NMR CTD B RNA RNA NMR C RNA RIG-I RNA RIG-I CTD RNA RD CTD RNA ATP RD RIG-I RNA IFN RNA RNA RNA RIG-I NMR Yoneyama, M., Kikuchi, M., Natsukawa, T., Shinobu, N., Imaizumi, T., Miyagishi, M., Taira, K., Akira, S., & Fujita, T.
5 ２ 生化学 第 巻 第９号 図３ RIG-I CTD の三次元構造 Ａ NMR によって解かれた RIG-I CTD の構造 β３から βまでの六つの β シート構造の上に 二つの α ヘ リックスをはさんで三つの β シートが乗った構造をとる 上下の構造から出ているループに四つのシステイ ン残基があり それを介して Zn イオンが結合していることが示唆されている Ｂ CTD の表面電荷を示し ている 溝状の構造に黒で示した正電荷が集中している ここでは示していないが この裏面には負電荷が 露出している Ｃ 三リン酸 ssrna の存在下で NMR のシグナルが消失したアミノ酸残基を示している 溝状の構造に集中していることがわかる ６ １ ９ ７のリジン残基をアラニンに置換した変異体 RIG-I がシグナル伝達能を失うことから この面で基質 RNA を認識していると考えられる ２ Nat. Immunol.,,７ ３ ７ ３ ７. ２ Yoneyama, M., Kikuchi, M., Matsumoto, K., Imaizumi, T., Miyagishi, M., Taira, K., Foy, E., Loo, Y.M., Gale, M., Jr., Akira, S., Yonehara, S., Kato, A., & Fujita, T. ２ J. Immunol., １ ７,２ １ ２. ３ Kato, H., Sato, S., Yoneyama, M., Yamamoto, M., Uematsu, S., Matsui, K., Tsujimura, T., Takeda, K., Fujita, T., Takeuchi, O., & Akira, S. ２ Immunity,２ ３,１ ９ ２. Kato, H., Takeuchi, O., Sato, S., Yoneyama, M., Yamamoto, M., Matsui, K., Uematsu, S., Jung, A., Kawai, T., Ishii, K.J., みにれびゆう Yamaguchi, O., Otsu, K., Tsujimura, T., Koh, C.S., Reis e Sousa, C., Matsuura, Y., Fujita, T., & Akira, S. ２ ６ Nature, １,１ １ １. Venkataraman, T., Valdes, M., Elsby, R., Kakuta, S., Caceres, G., Saijo, S., Iwakura, Y., & Barber, G.N. ２ ７ J. Immunol., １ ７,６ ６. ６ Saito, T., Hirai, R., Loo, Y.M., Owen, D., Johnson, C.L., Sinha, S.C., Akira, S., Fujita, T., & Gale, M., Jr. ２ ７ Proc. Natl. Acad. Sci. USA,１, ２ ７. ７ Hornung, V., Ellegast, J., Kim, S., Brzozka, K., Jung, A., Kato,
6 H., Poeck, H., Akira, S., Conzelmann, K.K., Schlee, M., Endres, S., & Hartmann, G.Science,,. Pichlmair, A., Schulz, O., Tan, C.P., Naslund, T.I., Liljestrom, P., Weber, F., & Reis e Sousa, C.Science,,. Kato, H., Takeuchi, O., Mikano-Satoh, E., Hirai, R., Kawai, T., Matsushita, K., Hiiragi, A., Dermody, T.S., Fujita, T., & Akira, S.J. Exp. Med.,,. Takahasi, K., Yoneyama, M., Nishihori, T., Hirai, R., Kumeta, H., Narita, R., Gale, M., Jr., Inagaki, F., & Fujita, T. Mol. Cell,,. Cui, S., Eisenacher, K., Kirchhofer, A., Brzozka, K., Lammens, A., Lammens, K., Fujita, T., Conzelmann, K.K., Krug, A., & Hopfner, K.P.Mol. Cell,,. Non-self RNA-sensing mechanism of RIG-I RNA helicase Mitsutoshi Yoneyama and Takashi Fujita Laboratory of Molecular Genetics, Institute for Virus Research, Kyoto University, Shogoinkawahara-cho, Sakyo-ku, Kyoto, Japan; PRESTO, Japan Science and Technology Agency, Honcho Kawaguchi, Saitama, Japan DNA REV Watson-Crick DNA DNA REV reversionless REV DNA DNA DNA pol δ pol ε DNA DNA DNA post-replication repair DNA RAD radiation sensitivity RAD E -E RAD -RAD proliferating cell nuclear antigen PCNA DNA translesion DNA synthesis, TLS RAD -RAD TLS DNA TLS DNA DNA REV rev Lawrence REV DNA DNA DNA dcmp XP-V XP-V damp pol η TLS Y- DNA XP-V pol η TLS damp Y- DNA pol η pol ι pol κ REV REV Y- dcmp datp dgtp dttp
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