東京大学大学院 薬学系研究科 蛋白構造生物学教室 Laboratory of Protein Structural Biology

研究業績   2015 | 2014 | 2013 | 2012 | 2011 | 2010   

Guanosine and its modified derivatives are endogenous ligands for TLR7.
Shibata T, Ohto U, Nomura S, Kibata K, Motoi Y, Zhang Y, Murakami Y, Fukui R, Ishimoto T, Sano S, Ito T, Shimizu T, Miyake K.
Int. Immunol. 28, 211-222

Analysis of the fine-tuning of cyanobacterial circadian phase by monochromatic light and long day conditions
Kobayashi T., Obana Y., Kuboi N., Kitayama Y., Hayashi S., Oka M., Wada N., Arita K., Shimizu T., Sato M., Kanaly R. and Kutsuna, S.
Plant Cell Phys. 57, 105-114

Novel helical assembly in arginine methyltransferase 8
Fuaki-Toma, S., Jun-Dal Kim, J.D., Park, K.E., Kuwabara, N. Shimizu, N., Krayukhina, E., Uchiyama, S., Fukamizu, A., Shimizu, T
J. Mol. Biol. 428, 1197-1208

Autoinhibition and relief mechanism by the proteolytic processing of Toll-like receptor 8
Tanji, H., Ohto, U., Motoi, Y., Shibata, T., Miyake, K., Shimizu, T.
Proc. Natl. Acad. Sci., USA 113, 3012-3017

Structural aspects of nucleic acid-sensing Toll-like receptors
Ohto, U. and Shimizu, T.
Biophysical Reviews 8, 33-43

Identification of a Human Toll-like Receptor (TLR) 8-specific Agonist and a Functional Pan-TLR Inhibitor in 2-Aminoimidazoles.
Beesu M, Caruso G, Salyer AC, Shukla NM, Khetani KK, Smith LJ, Fox LM, Tanji H, Ohto U,Shimizu T, David SA.
J. Med. Chem. 59, 3311-3330

NML-mediated rRNA base methylation links ribosomal subunit formation to cell proliferation in a p53-dependent manner
Waku T, Nakajima Y, Yokoyama W, Nomura N, Kako K, Kobayashi A, Shimizu T, Fukamizu A
J. Cell. Sci. 129, 2382-2393

Crystal structure of NOD2 and its implications in human disease
Maekawa S, Ohto U, Shibata, T, Miyake, K, Shimizu T
Nature comm. 7, 11813

Structure of IZUMO1–JUNO reveals sperm–oocyte recognition during mammalian fertilization
Ohto U, Ishida H, Krayukhina E, Uchiyama S, Inoue N, Shimizu T
Nature 534,566-569

Emerging roles of the processing of nucleic acids and Toll-like receptors in innate immune responses to nucleic acids
Miyake K, Shibata T, Ohto U, Shimizu T
J. Leukocyte Biol. , in press



DNase II-dependent DNA digestion is required for DNA sensing by TLR9
Chan M.P., Onji M., Fukui R., Kawane K., Shibata T., Saitoh S., Ohto U., Shimizu T., Barber G. and Miyake, K.
Nature com. 6, 5853

Targeting cell surface TLR7 for therapeutic intervention in autoimmune diseases
Kanno A., Tanimura N., Ishizaki M., Ohko K., Motoi Y., Onji M., Fukui R., Shimozato T., Yamamoto K., Shibata T., Sano S., Sugahara-Tobinai A., Takai T., Ohto U., Shimizu T., Saitoh S. and Miyake K.

Nature com. 6, 6119

Toll-like receptor 8 senses degradation products of single-stranded RNA
Tanji H., Ohto U., Shibata T., Taoka M., Yamauchi Y., Isobe T., Miyake K., and Shimizu T.
Nature Struc. Mol. Biol. 22, 109-115

Structural basis of CpG and inhibitory DNA recognition by Toll-like receptor 9
Ohto U., Shibata T., Tanji H., Ishida H., Krayukhina E., Uchiyama S., Miyake K. and Shimizu T.
Nature 520, 702-705

Structure of a Novel DNA-binding Domain of Helicase-like Transcription Factor (HLTF) and Its Functional Implication in DNA Damage Tolerance.
Hishiki A, Hara K, Ikegaya Y, Yokoyama H, Shimizu T, Sato M, Hashimoto H.
J. Biol. Chem. 290, 13215-13223

Crystal structure of human Roquin-2 and its complex with constitutive decay
element RNA
Sakurai S., Ohto U. and
Shimizu, T.
Acta Crystallogr.

The Imidazoquinoline Toll-like Receptor-7/8 Agonist Hybrid-2 Potently Induces Cytokine Production by Human Newborn and Adult Leukocytes
Ganapathi, L., Van Haren, S., Dowling, D.J., Bergelson, I., Shukla, N.M., Malladi, S.S., Balakrishna, R., Tanji, H., Ohto, U., Shimizu, T., David, S.A. and Levy, O.
PLoS One
10, e0134640

Structure-based Design of Human TLR8-specific Agonists with Augmented Potency and Adjuvanticity.
Beesu M, Caruso G, Salyer A, Khetani K, Sil D, Weerasinghe M, Tanji H, Ohto U, Shimizu T, David SA.
J. Med. Chem. 58, 7833-7849


64, 294-298

Toll-like receptorによる核酸の認識機構

医学のあゆみ 254, 541-545


The attenuated inflammation of MPL is due to the lack of CD14-dependent tight dimerization of the TLR4/MD2 complex at the plasma membrane
Tanimura N, Saitoh SI, Ohto U, Akashi-Takamura
S, Fujimoto Y, Fukase K, Shimizu T, Miyake K
Int. Immunol. 26, 307-314

Protein arginine methyltransferase 7 has a novel homodimer-like structure formed by tandem repeats
Hasegawa M, Toma-Fukai S, Kim JD, Fukamizu A, Shimizu T.
FEBS letters 588, 1942-1948

Structural basis of pharmacological chaperoning for human β-galactosidase
Suzuki H, Ohto U, Higaki K, Mena-Barragan T, Aguilar-Moncayo M, Mellet CO, Nanba E, M Garcia Fernandez J, Suzuki Y, Shimizu T.
J. Biol. Chem. 289, 14560-14568

Swi5-Sfr1 protein stimulates Rad51-mediated DNA strand exchange reaction through organization of DNA bases in the presynaptic filament.
Fornander LH, Renodon-Cornière A, Kuwabara N, Ito K, Tsutsui Y, Shimizu T, Iwasaki H, Nordén B, Takahashi M.
Nucleic Acid Res. 42, 2358-2365

Structure-Based Design of Novel Human Toll-like Receptor 8 Agonists
Hari Prasad Kokatla, Sil D, Tanji H, Ohto U, Subbalakshmi S. Malladi, Lauren M. Fox, Shimizu T and Sunil A. David
ChemMedChem 9, 719-723

Structure and function of Toll-like receptor 8
Ohto, U., Tanji, H., Shimizu, T.
Microbes and Infection 16, 273-282

Determinants of Activity at Human Toll-like Receptors 7 and 8: Quantitative Structure-Activity Relationship (QSAR) of Diverse Heterocyclic Scaffolds
Yoo E, Salunke D, Sil D, Guo X, Salyer A, Hermanson A, Kumar M, Malladi SS, Balakrishna R, Thompson WH, Tanji H, Ohto U, Shimizu T, David SA.
J. Med. Chem. 57, 7955-7970

実験医学 32, 1661-1665

Drug Design – Structure and ligand-based approaches  Merz Jr., K.M., Ringe D., Reynolds C.H.
ドラッグデザイン 構造とリガンドに基づくアプローチ  田之倉優、小島正樹 監訳
15章 プリンヌクレオシドホスホリラーゼを標的とした遷移状態類似体設計



A nonclassical vitamin D receptor pathway suppresses renal fibrosis. (2013)
Ito, I., Waku, T., Aoki, M. Abe, R., Nagai, Y., Watanabe, T., Nakajima,Y., Ohkido, I., Yokoyama, K., Miyachi, H., Shimizu, T., Murayama, A., Kishimoto , H., Nagasawa, K., Yanagisawa, J.

J. Clin. Invest. 123, 4579-4594

Impaired α-TTP-PIPs Interaction Underlies Familial Vitamin E Deficiency. (2013)

Kono N.*, Ohto U.*, Hiramatsu T., Urabe M., Uchida Y., Satow Y., and Arai H.
Science 340, 1106-1110 (* equally contributed)

TLR4-MD-2 complex is negatively regulated by an endogenous ligand, globotetraosylceramide. (2013)

Kondo Y., Ikeda K., Tokuda N., Nishitani C., Ohto U., Akashi-Takamura S., Ito Y.,Uchikawa M., Kuroki Y., Taguchi R., Miyake K., Zhang Q., Furukawa K., and Furukawa K.

Proc Natl Acad Sci U S A. 110, 4714-4719.

Structural reorganization of the Toll-like receptor8 dimer induced by agonistic ligands (2013)
Tanji H.*, Ohto U.*, Shibata T., Miyake K., and Shimizu T.

339, 1426-1429 (* equally contributed)

Structural basis for vitamin D receptor agonism by novel nonsecosteroidal ligands (2013)
Asano L., Ito I., Kuwabara N., Waku T., Yanagisawa J., Miyachi H. and Shimizu T.
FEBS letters 587, 957-963

Characterisation of an intrinsicallly disordered potein complex of Swi5-Sfr1 by ion mobility mass spectrometry and small-angle X-ray scattering (2013)
Saikusa K., Kuwabara N., Kokabu Y., Inoue Y., Sato M., Iwasaki H., Shimizu T., Ikeguchi M. and Akashi S.
Analyst 138, 1441-1449

Human TLR4 polymorphism D299G/T399I alters TLR4/MD-2 conformation and response to a weak ligand monophosphoryl lipid A (2013)
Yamakawa N.*, Ohto U.*, Akashi-Takamura S., Takahashi K., Saitoh S., Tanimura N., Suganami T., Ogawa Y., Shibata T., Shimizu T., and Miyake K.
Int. Immunol. 25, 45-52
(* equally contributed)

Serum amyloid A3 binds MD-2 to activate p38 and NF-κB pathways in a MyD88-dependent manner
Deguchi, A., Tomita, T., Omori, T., Komatsu, A., Ohto, U., Takahashi, S.,Tanimura, N., Akashi-Takamura, S., Miyake, K., & Maru, Y.
J. Immunol.191,1856-1864



結晶学会誌 55, 285-289

ライソゾーム病原因タンパク質β-ガラクトシターゼの構造基盤 (2013)

薬学雑誌 133, 509-517



Structural analyses of human Toll-like receptor 4 polymorphisms D299G and T399I (2012)
Ohto U., Yamakawa N., Akashi-Takamura S., Miyake K. and Shimizu T. 
J.Biol.Chem. 287, 40611-40617

Coagulation Factor X Activates Innate Immunity to Human Species C Adenovirus. (2012)

Doronin K, Flatt JW, Di Paolo NC, Khare R, Kalyuzhniy O, Acchione M, Sumida JP, Ohto U, Shimizu T, Akashi-Takamura S, Miyake K, Macdonald JW, Bammler TK, Beyer RP, Farin FM, Stewart PL, Shayakhmetov DM.
Science 338, 795-798

Crystallization and X-ray diffraction analysis of the ternary complex of the C-terminal domain of human REV1 in complex with REV7 bound to a REV3 fragment involved in translesion DNA synthesis (2012)

Kikuchi S, Hara K, Shimizu T, Sato M, Hashimoto H.

Acta Crystallogr F68, 962-964

Structural Basis of Recruitment of DNA Polymerase ζ by Interaction between REV1 and REV7 Proteins (2012)

Kikuchi S, Hara K, Shimizu T, Sato M, Hashimoto H.

J Biol Chem. 287, 33847-33852

basis for the inhibition of xyloglucan-specific endo-β-1,4-glucanase (XEG) by XEG-protein inhibitor (2012)
Yoshizawa, Y., Shimizu, T., Hirano, H., Sato, M., Hashimoto, H.
287, 18710-18716

Structural basis of species-specific endotoxin sensing by innate immune receptor TLR4/MD-2 (2012)
Ohto, U., Fukase, K., Miyake, K., and Shimizu, T
Proc. Natl. Acad. Sci., USA 109, 7421-7426

Saturated Fatty Acid and TLR Signaling Link β Cell Dysfunction and Islet Inflammation. (2012)
Eguchi, K., Manabe, I., Oishi-Tanaka, Y., Ohsugi, M., Kono, N., Ogata, F., Yagi, N., Ohto, U., Kimoto, M., Miyake, K., Tobe, K., Arai, H., Kadowaki, T., & Nagai, R.
Cell Metab. 15, 1-16.

Mechanistic insights into the activation of rad51-mediated strand exchange from the structure of a recombination activator, the swi5-sfr1 complex. (2012)
Kuwabara N, Murayama Y, Hashimoto H, Kokabu Y, Ikeguchi M, Sato M, Mayanagi K, Tsutsui Y, Iwasaki H, Shimizu T.
Structure 20, 440-449.

Peroxisome Proliferator-activatedreceptors (PPARs) have multiple binding points that accommodate ligands invarious conformations: Phenypropanoic acid-type PPAR ligands bind to PPAR indifferent conformations, depending on the subtype (2012)
Kuwabara N, Oyama T, Tomioka D, Ohashi M, Yanagisawa J, Shimizu T, Miyachi H
J. Med. Chem. 55, 893-902

Crystal Structure of Human β-Galactosidase: The Structural Basis of GM1 Gangliosidosis and Morquio B Diseases (2012)
Ohto U, Usui K, , Ochi T, ,Yuki K, Satow Y and Shimizu T
J. Biol. Chem. 287, 1801-1812

Expression, purification, crystallisation and preliminary X-ray crystallographic analysis of human β-Galactosidase (2012)
Usui K, Ohto U, Ochi T, Shimizu T, and Satow Y
Acta Crystallogr. F68, 73-77


The fission yeast Swi5-Sfr1 complex, an activator of Rad51 recombinase, forms an extremely elongated Dogleg-shaped structure. (2011)
Kokabu Y, Murayama Y, Kuwabara N, Oroguchi T, Hashimoto H, Tsutsui Y, Nozaki N, Akashi S, Unzai S, Shimizu T, Iwasaki H, Sato M, Ikeguchi M.
J Biol Chem. 286, 43569-76

Crystal Structures of Mouse and Human RP105/MD-1 Complexes Reveal Unique Dimer Organization of the Toll-Like Receptor Family. (2011)
Ohto U, Miyake K, Shimizu T.
J Mol Biol. 413, 815-825

Purification, crystallization and X-ray diffraction study of extracellular dermal glycoprotein from carrot and the inhibition complex that it forms with an endo-β-glucanase from Aspergillus aculeatus. (2011)
Yoshizawa T, Shimizu T, Hirano H, Sato M, Hashimoto H.
Acta Crystallogr. F67, 830-832

Crystal structure of basic 7S globulin, a XEGIP-like protein from soybean lacking inhibition activity against endo-?-glucanase (2011)
Yoshizawa, T., Shimizu, T., Yamabe, M., Taichi, M., Nishiuchi, Y., Shichijo, N., Unzai, S., Hirano, H., Sato, M., Hashimoto, H.
FEBS J. 278, 1944-1954

Purification, crystallization and X-ray diffraction study of basic 7S globulin from soybean. (2011)
Yoshizawa T, Hashimoto H, Shimizu T, Yamabe M, Shichijo N, Hanada K, Hirano H, Sato M.
Acta Crystallogr. F67, 87-89

Crystal structures of the SEp22 dodecamer, a Dps-like protein from Salmonella enterica subsp. enterica serovar Enteritidis. (2011)
Miyamoto, T., Asahina, Y., Miyazaki, S., Shimizu, H., Ohto, U., Noguchi, S. & Satow, Y.
Acta Crystallogr. F67, 17-22.


Crystal structure of human REV7 in complex with a human REV3 fragment and structural implication of the interaction between DNA polymerase zeta and REV1. (2010)
Hara, K., Hashimoto, H., Murakumo, Y., Kobayashi, S., Kogame, T., Unzai, S., Akashi, S., Takeda, S., Shimizu, T. & Sato, M
J Biol Chem. 285, 12299-12307.

Structure of the N-terminal regulatory domain of a plant NADPH oxidase and its functional implications. (2010)
Oda, T., Hashimoto, H., Kuwabara, N., Akashi, S., Hayashi, K., Kojima, C., Wong, H. L., Kawasaki, T., Shimamoto, K., Sato, M. & Shimizu, T.
J Biol Chem. 285, 1435-1445..

Structure and functional characterization of Vibrio parahaemolyticus thermostable direct hemolysin (TDH). (2010)
Yanagihara, I., Nakahira, K., Yamane, T., Kaieda, S., Mayanagi, K., Hamada, D., Fukui, T., Ohnishi, K., Kajiyama, S., Shimizu, T., Sato, M., Ikegami, T., Ikeguchi, M., Honda, T. & Hashimoto, H.
J Biol Chem. 285, 16267-74.

Crystallization and X-ray diffraction studies of DNA-free and DNA-bound forms of EcoO109I DNA methyltransferase (2010)
Iwamoto, M., Hishiki, A., Shimada, T., Imasaki, T., Tsuda, J., Kita, K., Shimizu, T., Sato, M. and Hashimoto, H.
Acta Crystallogr. F66, 1528-1530.

Crystal structure and functional implication of zinc-finger domain of Nanos. (2010)
Hashimoto, H., Hara, K., Hishiki, A., Kawaguchi, S., Shichijo, N., Nakamura, K., Unzai, S., Tamaru, Y., Shimizu, T. and Sato, M.
EMBO Reports 11, 848-853.

Isomerization mechanism of aspartate to isoaspartate implied by structures of Ustilago sphaerogena ribonuclease U2 complexed with adenosine 3'-monophosphate. (2010)
Noguchi, S.
Acta Crystallogr. D66, 843-849.

Crystal structure of mouse MD-1 with endogenous phospholipid bound in its cavity. (2010)
Harada, H., Ohto, U. & Satow, Y.
J Mol Biol. 400, 838-846.

Structural changes induced by the deamidation and isomerization of asparagine revealed by the crystal structure of Ustilago sphaerogena ribonuclease U2B. (2010)
Noguchi, S.
Biopolymers, 93, 1003-1010.

Peptide-binding sites as revealed by the crystal structures of the human Hsp40 Hdj1 C-terminal domain in complex with the octapeptide from human Hsp70. (2010)
Suzuki, H., Noguchi, S., Arakawa, H., Tokida, T., Hashimoto, M. & Satow, Y.
Biochemistry, 49, 8577-8584.

Expression, purification and crystallization of Swi5 and the Swi5-Sfr1 complex from fission yeast. (2010)
Kuwabara, N., Hashimoto, H., Yamada, N., Unzai, S., Ikeguchi, M., Sato, M., Murayama, Y., Iwasaki, H. & Shimizu, T.
Acta Crystallogr. F66, 1124-1126.

Purification, crystallization and preliminary X-ray crystallographic analysis of human heat shock protein 40, Hdj1, and its C-terminal peptide-binding domain. (2010)
Suzuki, H., Noguchi, S., Arakawa, H., Tokida, T., Hashimoto, M. & Satow, Y.
Acta Crystallogr. F66, 1591-1595.

Conformational variation revealed by the crystal structure of RNase U2A complexed with Ca ion and 2'-adenylic acid at 1.03 A resolution. (2010)
Noguchi, S.
Protein Peptide Lett. 17, 1559-1561.

転写 「入門 構造生物学」(2010)

共立出版 103-111