6JBT

Complex structure of toripalimab-Fab and PD-1

Summary for 6JBT

• Entry DOI: 10.2210/pdb6jbt/pdb
• Descriptor: Programmed cell death protein 1, Heavy chain, Light chain, ... (6 entities in total)
• Functional Keywords: toripalimab-fab, pd-1, glycosylation, complex structure, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 67055.62

Authors

Guo, L.,Tan, S.,Chai, Y.,Qi, J.,Gao, G.F.,Yan, J. (deposition date: 2019-01-26, release date: 2019-06-19, Last modification date: 2024-11-13)

Primary citation

Liu, H.,Guo, L.,Zhang, J.,Zhou, Y.,Zhou, J.,Yao, J.,Wu, H.,Yao, S.,Chen, B.,Chai, Y.,Qi, J.,Gao, G.F.,Tan, S.,Feng, H.,Yan, J.
Glycosylation-independent binding of monoclonal antibody toripalimab to FG loop of PD-1 for tumor immune checkpoint therapy.
Mabs, 11:681-690, 2019

PubMed Abstract: Monoclonal antibody (mAb)-based blockade of programmed cell death 1 (PD-1) or its ligand to enable antitumor T-cell immunity has been successful in treating multiple tumors. However, the structural basis of the binding mechanisms of the mAbs and PD-1 and the effects of glycosylation of PD-1 on mAb interaction are not well understood. Here, we report the complex structure of PD-1 with toripalimab, a mAb that is approved by China National Medical Products Administration as a second-line treatment for melanoma and is under multiple Phase 1-Phase 3 clinical trials in both China and the US. Our analysis reveals that toripalimab mainly binds to the FG loop of PD-1 with an unconventionally long complementarity-determining region 3 loop of the heavy chain, which is distinct from the known binding epitopes of anti-PD-1 mAbs with structural evidences. The glycan modifications of PD-1 could be observed in three potential N-linked glycosylation sites, while no substantial influences were detected to the binding of toripalimab. These findings benefit our understanding of the binding mechanisms of toripalimab to PD-1 and shed light for future development of biologics targeting PD-1. Atomic coordinates have been deposited in the Protein Data Bank under accession code 6JBT.

PubMed: 30892132
DOI: 10.1080/19420862.2019.1596513

Experimental method

X-RAY DIFFRACTION (2.47 Å)