3X3F

TRAIL-R2 Extracellular Region Complexed to a Fab fragment from Human Agonist Antibody KMTR2

3X3F の概要

• エントリーDOI: 10.2210/pdb3x3f/pdb
• 関連するPDBエントリー: 3X3G
• 分子名称: Heavy chain of KMTR2, Light chain of KMTR2, Tumor necrosis factor receptor superfamily member 10B, ... (7 entities in total)
• 機能のキーワード: trail-r2, agonist antibody, apoptosis-immune system complex, apoptosis/immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 64943.57

構造登録者

Tamada, T. (登録日: 2015-01-20, 公開日: 2015-12-23, 最終更新日: 2024-10-30)

主引用文献

Tamada, T.,Shinmi, D.,Ikeda, M.,Yonezawa, Y.,Kataoka, S.,Kuroki, R.,Mori, E.,Motoki, K.
TRAIL-R2 Superoligomerization Induced by Human Monoclonal Agonistic Antibody KMTR2
Sci Rep, 5:17936-17936, 2015

PubMed Abstract: The fully human monoclonal antibody KMTR2 acts as a strong direct agonist for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 2 (TRAIL-R2), which is capable of inducing apoptotic cell death without cross-linking. 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 complementarity-determining region 2 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, although it retained its antigen-binding 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.

PubMed: 26672965
DOI: 10.1038/srep17936

実験手法

X-RAY DIFFRACTION (2.1 Å)