The structural analysis of the onset mechanism of cryopyrin-associated periodic syndrome

• Project/Area Number: 26461576
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Gifu University
• Principal Investigator: Ohnishi Hidenori 岐阜大学, 医学部附属病院, 講師 (60381620)
• Research Collaborator: TOCHIO HIDEHITO 京都大学 ; KIMURA TAKESHI 岐阜大学
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 自己炎症性疾患 / 自然免疫

Outline of Final Research Achievements

The purpose of this study was the recombinant protein expression, purification and molecular analyses of human NLRP3, in order to analysis the onset mechanism of cryopyrin-associated periodic syndrome. We tried to use the insect cell protein expression systems (silkworm or SF9 cells) with the various protein expression constructs. The protein expression of NLRP3 variants was confirmed, but they were insoluble. Therefore, we could not obtain the suitable protein samples for analyzing the function and structure.
In conclusion, our study revealed the quite difficulty of the large-scale protein purification of human NLRP3.

Research Products

• [Journal Article] A Japanese family case with juvenile onset Behçet's disease caused by TNFAIP3 mutation (2017)
  • Author(s): Ohnishi H, Kawamoto N, Seishima M, Ohara O, Fukao T.
  • Journal Title: Allergology International Volume: 66 Issue: 1 Pages: 146-148
  • DOI: 10.1016/j.alit.2016.06.006
  • NAID: 130005308497
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pyoderma Gangrenosum, Acne and Suppurative Hidradenitis Syndrome Treated with Granulocyte and Monocyte Adsorption Apheresis. (2016)
  • Author(s): Mizutani Y, Okano T, Takahashi T, Ohnishi H, Ohara O, Sano A, Seishima M.
  • Journal Title: Acta Derm Venereol. Volume: － Issue: 2 Pages: 275-276
  • DOI: 10.2340/00015555-2507
  • Peer Reviewed
• [Journal Article] Selective Labeling of Proteins on Living Cell Membranes Using Fluorescent Nanodiamond Probes. (2016)
  • Author(s): Shingo Sotoma, Jun Iimura, Ryuji Igarashi, Koichiro M. Hirosawa, Hidenori Ohnishi, Shin Mizukami, Kazuya Kikuchi, Takahiro K. Fujiwara, Masahiro Shirakawa and Hidehito Tochio
  • Journal Title: Nanomaterials Volume: 6 Issue: 4 Pages: 56-56
  • DOI: 10.3390/nano6040056
  • NAID: 120005848250
  • Peer Reviewed / Open Access
• [Journal Article] Alanine-scanning mutagenesis of human signal transducer and activator of transcription 1 to estimate loss- or gain-of-function variants (2016)
  • Author(s): Kagawa R, Fujiki R, Tsumura M, Sakata S, Nishimura S,Itan Y, Kong XF, Kato Z, Ohnishi H, Hirata O, Saito S, Ikeda M,Baghdadi JE, Bousfiha A, Fujiwara K, Oleastro M, Yancoski J,Perez L, Danielian S, Ailal F, Takada H, Hara T, Anne Puel A, Boisson-Dupuis S, Bustamante J, Casanova JL, Ohara O, Okada S, Masao Kobayashi M.
  • Journal Title: J Allergy Clin Immunol. Volume: － Issue: 1 Pages: 232-241
  • DOI: 10.1016/j.jaci.2016.09.035
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Familial Mediterranean fever variant with repeated atypical skin eruptions (2015)
  • Author(s): Takahashi T, Fujisawa T, Kimura M, Ohnishi H, Seishima M
  • Journal Title: J Dermatol Volume: 42 Issue: 9 Pages: 903-905
  • DOI: 10.1111/1346-8138.12929
  • Peer Reviewed / Open Access
• [Journal Article] Mondini dysplasia with recurrent bacterial meningitis caused by three different pathogens. (2015)
  • Author(s): Shikano H, Ohnishi H, Fukutomi H, Ito K, Morimoto M, Teramoto T, Aoki M, Nishihori T, Akeda Y, Oishi K, Fukao T.
  • Journal Title: Pediatr Int. Volume: 57 Issue: 6 Pages: 1192-1195
  • DOI: 10.1111/ped.12731
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] IgGサブクラス欠損症およびIgA欠損症 (2015)
  • Author(s): 大西秀典, 金子英雄
  • Journal Title: 小児内科 Volume: 47 Pages: 718-721
• [Journal Article] Merkel cell polyomavirus-positive Merkel cell carcinoma in a patient with epidermodysplasia verruciformis (2015)
  • Author(s): Mizuno Y, et al. 8名
  • Journal Title: Acta Derm Venereol Volume: 95 Issue: 1 Pages: 98-99
  • DOI: 10.2340/00015555-1868
  • Peer Reviewed / Open Access
• [Journal Article] The structural basis for receptor recognition of human interleukin-18 (2014)
  • Author(s): Naotaka Tsutsumi, Takeshi Kimura, Kyohei Arita, Mariko Ariyoshi, Hidenori Ohnishi, Takahiro Yamamoto, Xiaobing Zuo, Katsumi Maenaka, Enoch Y. Park, Naomi Kondo, Masahiro Shirakawa, Hidehito Tochio and Zenichiro Kato
  • Journal Title: Nat. Commun. Volume: 5 5340 Issue: 1 Pages: 1-13
  • DOI: 10.1038/ncomms6340
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Purification, crystallization and preliminary X-ray crystallographic analysis of human IL-18 and its extracellular complexes (2014)
  • Author(s): Takeshi Kimura, Naotaka Tsutsumi, Kyohei Arita, Mariko Ariyoshi, Hidenori Ohnishi, Naomi Kondo, Masahiro Shirakawa, Zenichiro Kato and Hidehito Tochio
  • Journal Title: Acta Crystallogr. Sect. F Struct. Biol. Commun. Volume: 70 Issue: 10 Pages: 1351-1356
  • DOI: 10.1107/s2053230x14016926
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Clinical and genetic characterization of Japanese sporadic cases of periodic Fever, aphthous stomatitis, pharyngitis and adenitis syndrome from a single medical center in Japan. (2014)
  • Author(s): Kubota K, Ohnishi H, Teramoto T, Kawamoto N, Kasahara K, Ohara O, Kondo N.
  • Journal Title: J Clin Immunol. Volume: 34 Issue: 5 Pages: 584-593
  • DOI: 10.1007/s10875-014-0043-2
  • Peer Reviewed
• [Journal Article] A complement factor B mutation in a large kindred with atypical hemolytic uremic syndrome. (2014)
  • Author(s): Funato M, Uemura O, Ushijima K, Ohnishi H, Orii K, Kato Z, Yamakawa S, Nagai T, Ohara O, Kaneko H, Kondo N.
  • Journal Title: J Clin Immunol. Volume: 34 Issue: 6 Pages: 691-695
  • DOI: 10.1007/s10875-014-0058-8
  • Peer Reviewed
• [Patent(Industrial Property Rights)] インターロイキン-18活性阻害剤 (2016)
  • Inventor(s): 大西秀典、木村豪、加藤善一郎、杤尾豪人、堤尚孝、横田歩
  • Industrial Property Rights Holder: 京都大学、岐阜大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-12-09
  • Overseas
• [Patent(Industrial Property Rights)] インターロイキン－１８活性阻害剤 (2015)
  • Inventor(s): 杤尾豪人、堤尚孝、横田歩、大西秀典、木村豪、加藤善一郎
  • Industrial Property Rights Holder: 杤尾豪人、堤尚孝、横田歩、大西秀典、木村豪、加藤善一郎
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-242091
  • Filing Date: 2015-12-11