2001 年度実績報告書

好中球活性化因子LECT2レセプターのX線結晶構造解析

研究課題

研究課題/領域番号	13033045
研究種目	特定領域研究(A)
研究機関	国立感染症研究所
研究代表者	鈴木和男国立感染症研究所, 生物活性物質部, 研究員 (20192130)
研究分担者	山越智国立感染症研究所, 生物活性物質部, 研究員 (00212283)
キーワード	サイトカイン / レセプター / X線結晶構造解析 / 遺伝子多型 / 好中球 / LECT2 / NMR / 血管炎
研究概要	慢性関節リュウマチ患者において、好中球活性化サイトカインLECT2(leukocyte cell-derived chemotaxin2)の58番目のVal残基がIle残基に置換されている患者ほど、疾病の重篤度が高いことが明らかになっている。そこで、本研究では、LECT2とそのレセプター相互関係を調べるために、LECT2の高次構造解析およびそのレセプターLECT2の高次構造解析を目的とした。すなわち、LECT2の機能発現による58番目のVal残基のメチレン基1つ分の役割がいかに重要かを構造解析およびレセブター相互関係から明らかにする。 1.NMRを用いた高次構造解析においては、安定同位体標識したサンプル調製法の確立とNMR測定とスペクトルの解析を行った。現在までのところ、主鎖のスペクトル帰属はほぼ完了し、二次構造情報まで得られた。 2.X線結晶構造解析においては、動物細胞を用いた発現系の導入とサンプル調製法を確立した。X線結晶構造解析を目指した結晶化を試みた結果、結晶が得られ、X線を当てた結果、分解能1.8Åのデータが得られた。

研究成果
(13件)

すべてその他

すべて文献書誌 (13件)

[文献書誌] Aratani, Y: "Critical role of myeloperoxidase and NADPH-oxidase in high-burden systemic infection of mice with Candida albicans"J.Infect.Dis.. (in press).
[文献書誌] A.Ishida-Okawara: "Contribution of myeloperoxidase to coronary artery vasculitis associated with MPO-ANCAproduction"Inflammation.. 25. 381-387 (2001)
[文献書誌] W.K.Dawson: "Aphysical origin for functional domain structure in nucleic acids as evidenced by cross linking entropy. partII"J.Theor.Biol.. 213. 387-412 (2001)
[文献書誌] W.K.Dawson: "Aphysical origin for functional domain structure in nucleic acids as evidenced by cross linking entropy. partI"J.Theor.Biol.. 213. 359-386 (2001)
[文献書誌] K.Suzuki: "Neutrophil functions of patients with vasculitis related to MPO-ANCA"International Journal of Hematology. 74. 134-143 (2001)
[文献書誌] K.Suzuki: "Neutrophil functions of patients with vasclitis related to MPO-ANCA(Review)"International Journal of Hematology. 74. 134-143 (2001)
[文献書誌] K.Suzuki: "Bioinaging of chemotaxis/migration and adhesion for transmigration of neutrophils with special reference to neutrophil functions(Review)"Bioimages. 9. 1-14 (2001)
[文献書誌] Y.Segawa: "Possible changes in expression of a chemotaxin LECT2 mRNA in mouse livers after concanavalin A-induced hepatic injury"Biol.Pharm.Bull.. 24. 425-428 (2001)
[文献書誌] Y.Aratani: "Differential host susceptibility to pulmonary infections with bacteria and fungi in mice deficient in myeloperoxidase"J.Infectious Diseases. 182. 1276-1279 (2000)
[文献書誌] Y.Kawai: "Modulation of chemotaxis, O_<2-> production and myeloperoxidase release from human polymorphonuclear leukocytes by the ornithine-containing lipid and serineglycine-containing lipid of Flavobacterium"FEMS Immunol. Med. Microbiol.. 28. 205-209 (2000)
[文献書誌] Kameoka, Y.: "Val58Ile polymorphism of the neutrophil chemoattractant LECT2 and rheumatoid arthritis in the Japanese population"Arthritis and Rheumatism. 43. 1419-1420 (2000)
[文献書誌] Fujii, A.: "Epitope analysis of myeloperoxidase-specific anti-neutrophil Cytoplasmic antibody(MPO-ANCA)associated glomerulonephritis"Clin. Nephrology. 53. 242-252 (2000)
[文献書誌] K.Suzuki: "The Peroxidase Multigene Family of Enzymes."Nauseef W.M.. 145-149 (2000)

2001 年度 実績報告書

好中球活性化因子LECT2レセプターのX線結晶構造解析

研究代表者

鈴木 和男 国立感染症研究所, 生物活性物質部, 研究員 (20192130)

研究成果

[文献書誌] Aratani, Y: "Critical role of myeloperoxidase and NADPH-oxidase in high-burden systemic infection of mice with Candida albicans"J.Infect.Dis.. (in press).

[文献書誌] A.Ishida-Okawara: "Contribution of myeloperoxidase to coronary artery vasculitis associated with MPO-ANCAproduction"Inflammation.. 25. 381-387 (2001)

[文献書誌] W.K.Dawson: "Aphysical origin for functional domain structure in nucleic acids as evidenced by cross linking entropy. partII"J.Theor.Biol.. 213. 387-412 (2001)

[文献書誌] W.K.Dawson: "Aphysical origin for functional domain structure in nucleic acids as evidenced by cross linking entropy. partI"J.Theor.Biol.. 213. 359-386 (2001)

[文献書誌] K.Suzuki: "Neutrophil functions of patients with vasculitis related to MPO-ANCA"International Journal of Hematology. 74. 134-143 (2001)

[文献書誌] K.Suzuki: "Neutrophil functions of patients with vasclitis related to MPO-ANCA(Review)"International Journal of Hematology. 74. 134-143 (2001)

[文献書誌] K.Suzuki: "Bioinaging of chemotaxis/migration and adhesion for transmigration of neutrophils with special reference to neutrophil functions(Review)"Bioimages. 9. 1-14 (2001)

[文献書誌] Y.Segawa: "Possible changes in expression of a chemotaxin LECT2 mRNA in mouse livers after concanavalin A-induced hepatic injury"Biol.Pharm.Bull.. 24. 425-428 (2001)

[文献書誌] Y.Aratani: "Differential host susceptibility to pulmonary infections with bacteria and fungi in mice deficient in myeloperoxidase"J.Infectious Diseases. 182. 1276-1279 (2000)

[文献書誌] Y.Kawai: "Modulation of chemotaxis, O_<2-> production and myeloperoxidase release from human polymorphonuclear leukocytes by the ornithine-containing lipid and serineglycine-containing lipid of Flavobacterium"FEMS Immunol. Med. Microbiol.. 28. 205-209 (2000)

[文献書誌] Kameoka, Y.: "Val58Ile polymorphism of the neutrophil chemoattractant LECT2 and rheumatoid arthritis in the Japanese population"Arthritis and Rheumatism. 43. 1419-1420 (2000)

[文献書誌] Fujii, A.: "Epitope analysis of myeloperoxidase-specific anti-neutrophil Cytoplasmic antibody(MPO-ANCA)associated glomerulonephritis"Clin. Nephrology. 53. 242-252 (2000)

[文献書誌] K.Suzuki: "The Peroxidase Multigene Family of Enzymes."Nauseef W.M.. 145-149 (2000)

2001 年度実績報告書

鈴木和男国立感染症研究所, 生物活性物質部, 研究員 (20192130)