Structural biology of dioxin receptor

• Project/Area Number: 25650029
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry
• Research Institution: The University of Tokyo
• Principal Investigator: OHTO Umeharu 東京大学, 薬学研究科(研究院), 講師 (90451856)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ダイオキシン / 環境汚染 / 芳香族炭化水素受容体

Outline of Final Research Achievements

For crystallogaraphic analysis of dioxin receptor, we constructed expression system of AhR and its coreceptor ARNT. We examined various sources of AhR/ARNT genes, expression hosts, and optimum regions for expression. We established purification protocol for AhR/ARNT. We conducted DNA binding experiments and crystallization screening using purified AhR/ARNT.

Research Products

• [Journal Article] Toll-like receptor 8 senses degradation products of single-stranded RNA. (2015)
  • Author(s): Tanji H, Ohto U, Shibata T, Taoka M, Yamauchi Y, Isobe T, Miyake K,
  • Journal Title: Nat Struct Mol Biol. Volume: 22 Issue: 2 Pages: 109-115
  • DOI: 10.1038/nsmb.2943
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Determinants of activity at human Toll-like receptors 7 and 8: quantitative structure-activity (2014)
  • Author(s): Yoo E, Salunke DB, Sil D, Guo X, Salyer AC, Hermanson AR, Kumar M,
  • Journal Title: J Med Chem. Volume: 57 Issue: 19 Pages: 7955-7970
  • DOI: 10.1021/jm500744f
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Structural basis of pharmacological chaperoning for human β-galactosidase (2014)
  • Author(s): Suzuki H, et al.
  • Journal Title: J. Biol. Chem. Volume: 289 Issue: 21 Pages: 14560-14568
  • DOI: 10.1074/jbc.m113.529529
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Structure-Based Design of Novel Human Toll-like Receptor 8 Agonists. (2014)
  • Author(s): Kokatla, H. P., Sil, D., Tanji, H., Ohto, U., Malladi, S. S., Fox, L. M., Shimizu, T., & David, S. A.
  • Journal Title: ChemMedChem. Volume: 9 Issue: 4 Pages: 713-723
  • DOI: 10.1002/cmdc.201300573
  • Peer Reviewed
• [Journal Article] Structure and function of toll-like receptor 8. (2014)
  • Author(s): Ohto, U., Tanji, H., & Shimizu, T.
  • Journal Title: Microbes Infect. Volume: 16 Issue: 4 Pages: 273-282
  • DOI: 10.1016/j.micinf.2014.01.007
  • Peer Reviewed
• [Journal Article] Impaired α-TTP-PIPs interaction underlies familial vitamin E deficiency. (2013)
  • Author(s): Kono N, Ohto U, Hiramatsu T, Urabe M, Uchida Y, Satow Y, Arai H.
  • Journal Title: Science Volume: 340 Issue: 6136 Pages: 1106-1110
  • DOI: 10.1126/science.1233508
  • NAID: 110009807290
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Serum Amyroid A3 binds MD-2 to activates p38 and NF-kB pathway in a MyD88-dependent manner (2013)
  • Author(s): Deguchi A, Tomita T, Omori T, Komatsu A, Ohto U, Takahashi S, Tanimura N, Akashi-Takamura S, Miyake K, Maru Y
  • Journal Title: J Immunol Volume: 191(4) Issue: 4 Pages: 1856-1864
  • DOI: 10.4049/jimmunol.1201996
  • Peer Reviewed
• [Presentation] Toll様受容体8(TLR8)と一本鎖RNA複合体の結晶構造 (2015)
  • Author(s): 丹治裕美、大戸梅治、柴田琢磨、田岡万悟、山内芳雄、礒邊俊明、三宅健介、清水敏之
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] 自然免疫受容体NOD2の結晶構造解析 (2015)
  • Author(s): 前川早貴子、大戸梅治、清水敏之
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] Structural study of Toll-like receptor 8 recognizing viral single stranded RNA (2014)
  • Author(s): Umeharu Ohto
  • Organizer: The International Symposium ‘Molecular basis of host cell competency in virus infection’ 2014
  • Place of Presentation: Yokohama
  • Year and Date: 2014-11-08 – 2014-11-09
  • Invited
• [Presentation] 自然免疫系Toll様受容体の構造生物学研究 (2014)
  • Author(s): 大戸梅治、清水敏之
  • Organizer: 第87回日本生化学会年会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] Structural studies of nucleic acid sensing Toll-like receptor (2014)
  • Author(s): U. Ohto, H. Tanji, T. Shibata, K. Miyake, and T. Shimizu
  • Organizer: 23rd Congress and General Assembly of The International Union of Crystallography (IUCr 2014)
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2014-08-05 – 2014-08-12
• [Presentation] TLR8と一本鎖RNAとの複合体の結晶構造 (2014)
  • Author(s): 丹治裕美、大戸梅治、柴田琢磨、三宅健介、清水敏之
  • Organizer: 第14回日本蛋白質科学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-06-25 – 2014-06-27
• [Presentation] Crystal structures of human Toll-like receptor 8 (2013)
  • Author(s): U. Ohto, H. Tanji, T. Shibata, K. Miyake, and T. Shimizu
  • Organizer: 4th International Symposium on Diffraction Structural Biology 2013
  • Place of Presentation: Nagoya
• [Presentation] Structural basis for species-specific endotoxin recognition by TLR4/MD-2 (2013)
  • Author(s): U. Ohto, K. Fukase, K. Miyake, and T. Shimizu
  • Organizer: ICSG2013-SLS
  • Place of Presentation: Sapporo