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TRAIL-R2 Superoligomerization Induced by Human Monoclonal Agonistic Antibody KMTR2
https://repo.qst.go.jp/records/72112
https://repo.qst.go.jp/records/72112b6ab9463-b247-4a87-a0b4-3a7d7a1e9be2
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2017-01-05 | |||||
| タイトル | ||||||
| タイトル | TRAIL-R2 Superoligomerization Induced by Human Monoclonal Agonistic Antibody KMTR2 | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
玉田, 太郎
× 玉田, 太郎× 新見, 大輔(協和発酵キリン株式会社 創薬技術研究所)× 池田, 昌弘(協和発酵キリン株式会社 免疫アレルギー研究所)× 森, 英治(協和発酵キリン株式会社 研究開発企画部)× 元木, 一宏(協和発酵キリン株式会社 がん研究所)× 玉田 太郎 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | The fully human monoclonal antibody KMTR2 acts as a strong direct agonist for TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2). To investigate the mechanism of direct agonistic activity induced by KMTR2, the crystal structure of the extracellular region of TRAIL-R2 and a Fab fragment derived from KMTR2 (KMTR2-Fab) was determined to 2.1 Å resolution. Two KMTR2-Fabs assembled with the CDR2 region of the light chain via two-fold crystallographic symmetry, suggesting that the KMTR2-Fab assembly tended to enhance TRAIL-R2 oligomerization. A single mutation at Asn53 to Arg located at the two-fold interface in the KMTR2 resulted in a loss of its apoptotic activity. These results indicate that the strong agonistic activity, such as apoptotic signaling and tumor regression, induced by KMTR2 is attributed to TRAIL-R2 superoligomerization induced by the interdimerization of KMTR2. | |||||
| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 第5回回折構造生物国際シンポジウム(ISDSB2016) | |||||
| 発表年月日 | ||||||
| 日付 | 2016-08-08 | |||||
| 日付タイプ | Issued | |||||
