7CGW

Complex structure of PD-1 and tislelizumab Fab

7CGW の概要

• エントリーDOI: 10.2210/pdb7cgw/pdb
• 分子名称: Heavy chain of tislelizumab Fab, Light chain of tislelizumab Fab, Programmed cell death protein 1, ... (4 entities in total)
• 機能のキーワード: tislelizumab, pd-1, antibody, antitumor protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 131561.07

構造登録者

Hong, Y.,Feng, Y.C.,Liu, Y. (登録日: 2020-07-02, 公開日: 2021-04-07, 最終更新日: 2024-11-13)

主引用文献

Hong, Y.,Feng, Y.,Sun, H.,Zhang, B.,Wu, H.,Zhu, Q.,Li, Y.,Zhang, T.,Zhang, Y.,Cui, X.,Li, Z.,Song, X.,Li, K.,Liu, M.,Liu, Y.
Tislelizumab uniquely binds to the CC' loop of PD-1 with slow-dissociated rate and complete PD-L1 blockage.
Febs Open Bio, 11:782-792, 2021

PubMed Abstract: Programmed cell death protein 1 (PD-1), an immune checkpoint receptor expressed by activated T, B, and NK cells, is a well-known target for cancer immunotherapy. Tislelizumab (BGB-A317) is an anti-PD-1 antibody that has recently been approved for treatment of Hodgkin's lymphoma and urothelial carcinoma. Here, we show that tislelizumab displayed remarkable antitumor efficacy in a B16F10/GM-CSF mouse model. Structural biology and Surface plasmon resonance (SPR) analyses revealed unique epitopes of tislelizumab, and demonstrated that the CC' loop of PD-1, a region considered to be essential for binding to PD-1 ligand 1 (PD-L1) but not reported as targeted by other therapeutic antibodies, significantly contributes to the binding of tislelizumab. The binding surface of tislelizumab on PD-1 overlaps largely with that of the PD-L1. SPR analysis revealed the extremely slow dissociation rate of tislelizumab from PD-1. Both structural and functional analyses align with the observed ability of tislelizumab to completely block PD-1/PD-L1 interaction, broadening our understanding of the mechanism of action of anti-PD-1 antibodies.

PubMed: 33527708
DOI: 10.1002/2211-5463.13102

実験手法

X-RAY DIFFRACTION (3.2 Å)