6J15
Complex structure of GY-5 Fab and PD-1
Summary for 6J15
| Entry DOI | 10.2210/pdb6j15/pdb |
| Descriptor | Programmed cell death protein 1, GY-5 heavy chain Fab, GY-5 light chain Fab, ... (6 entities in total) |
| Functional Keywords | tumor immunotherapy, complex structure, fg loop, immune system |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 124296.08 |
| Authors | |
| Primary citation | 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 Cited by 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: 30952089DOI: 10.1016/j.isci.2019.03.017 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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