7DR4

Complex of anti-human IL-2 antibody and human IL-2

7DR4 の概要

• エントリーDOI: 10.2210/pdb7dr4/pdb
• 分子名称: anti-human IL-2 antibody, mouse Ig G, heavy chain, anti-human IL-2 antibody, mouse Ig G, kappa chain, Interleukin-2, ... (4 entities in total)
• 機能のキーワード: complex, human il-2, antibody, tcell, protein binding, immune system
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 252251.56

構造登録者

Kim, M.S.,Kim, J.E. (登録日: 2020-12-25, 公開日: 2021-04-14, 最終更新日: 2024-11-06)

主引用文献

Kim, J.,Lee, J.Y.,Park, S.Y.,Lee, Y.J.,Kim, M.S.
Crystal structure of human interleukin-2 in complex with TCB2, a new antibody-drug candidate with antitumor activity.
Oncoimmunology, 10:1899671-1899671, 2021

PubMed Abstract: Immunotherapy via interleukin-2 (IL-2) mediated activation of anti-tumor immune response is a promising approach for cancer treatment. The multi-potent cytokine, IL-2 has a central role in immune cell activation and homeostasis. Since IL-2 preferentially activates immunosuppressive T regulatory cells by IL-2Rα dependent manner, blocking IL-2:IL-2Rα interaction is a key to amplify the IL-2 activity in effector T cells toward anti-tumor response. Anti-IL-2 monoclonal antibodies are good candidates to control the IL-2:IL-2Rα interaction. In a previous study, we developed a new IL-2Rα mimetic antibody, TCB2, and showed that the human IL-2(hIL-2):TCB2 complex can stimulate T effector cells specifically and elicit potent anti-cancer immunotherapeutic effect, especially when administered in combination with immune checkpoint inhibitors. To understand the molecular mechanism, we determined the crystal structure of TCB2-Fab in a complex with hIL-2 at 2.5 Å resolution. Our structural analysis reveals that TCB2 binds to the central area of the hIL-2Rα binding region on hIL-2, and binding angle and epitope are different from previously known hIL-2Rα mimicking antibody NARA1 which recognizes the top part of hIL-2. TCB2 binding to hIL-2 also induces an allosteric effect that increases the affinity for the hetero-dimeric hIL-2 receptor, IL-2R(β + γ), on effector T cells.

PubMed: 33796411
DOI: 10.1080/2162402X.2021.1899671

実験手法

X-RAY DIFFRACTION (2.49 Å)