6J15

Complex structure of GY-5 Fab and PD-1

6J15 の概要

• エントリーDOI: 10.2210/pdb6j15/pdb
• 分子名称: Programmed cell death protein 1, GY-5 heavy chain Fab, GY-5 light chain Fab, ... (6 entities in total)
• 機能のキーワード: tumor immunotherapy, complex structure, fg loop, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 124296.08

構造登録者

Chen, D.,Tan, S.,Zhang, H.,Wang, H.,Chai, Y.,Qi, J.,Yan, J.,Gao, G.F. (登録日: 2018-12-27, 公開日: 2019-11-06, 最終更新日: 2023-11-22)

主引用文献

Chen, D.,Tan, S.,Zhang, H.,Wang, H.,He, W.,Shi, R.,Tong, Z.,Zhu, J.,Cheng, H.,Gao, S.,Chai, Y.,Qi, J.,Xiao, M.,Yan, J.,Gao, G.F.
The FG Loop of PD-1 Serves as a "Hotspot" for Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy.
Iscience, 14:113-124, 2019

PubMed Abstract: Programmed cell death 1 (PD-1)/PD-1 ligand-1 (PD-L1)-blocking monoclonal antibodies (mAbs) have taken center stage for tumor immune checkpoint therapy. Identification of the "hotspots" on PD-1 for mAbs will help to develop next-generation oral deliverable agents with long-lasting efficacy. Here, we identified two PD-1-targeting mAbs, GY-5 and GY-14, with PD-1/PD-L1-blocking efficacy. Complex structural information revealed that both mAbs mainly bind to the FG loop of PD-1, which also contributes multiple interactions with PD-L1. The FG loop adopts substantially varied conformations upon binding to different mAbs, providing a novel targetable region for the development of PD-1-specific biologics and small chemical molecules. Glycosylation modifications of PD-1 could be observed in three of the four potential N-linked glycosylation sites. However, the binding of GY-5 and GY-14 to PD-1 was not affected by glycosylation. These findings broaden our understanding of the mechanism of anti-PD-1 mAbs and provide insight into the development of agents targeting PD-1.

PubMed: 30952089
DOI: 10.1016/j.isci.2019.03.017

実験手法

X-RAY DIFFRACTION (2.6 Å)