7BXA

Crystal structure of PD-1 in complex with tislelizumab Fab

7BXA の概要

• エントリーDOI: 10.2210/pdb7bxa/pdb
• 分子名称: Programmed cell death protein 1, heavy chain, light chain (3 entities in total)
• 機能のキーワード: pd-1, tislelizumab, immune checkpoint, antibody, 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: 126092.27

構造登録者

Heo, Y.S.,Lee, S.H.,Lim, H.,Lee, H.T.,Kim, Y.J.,Park, E.B. (登録日: 2020-04-18, 公開日: 2020-06-10, 最終更新日: 2024-11-13)

主引用文献

Lee, S.H.,Lee, H.T.,Lim, H.,Kim, Y.,Park, U.B.,Heo, Y.S.
Crystal structure of PD-1 in complex with an antibody-drug tislelizumab used in tumor immune checkpoint therapy.
Biochem.Biophys.Res.Commun., 527:226-231, 2020

PubMed Abstract: Blocking of the interaction between Programmed cell death 1 (PD-1) and its ligand PD-L1 by monoclonal antibodies has elicited unprecedented therapeutic benefits and achieved a major breakthrough in immunotherapy of multiple types of tumors. Here, we determined the crystal structure of PD-1 in complex with the Fab fragment of tislelizumab. This monoclonal antibody was approved in December 2019 by the China National Medical Product Administration for Hodgkin's lymphoma and is under multiple clinical trials in China and the US. While the three complementarity determining regions (CDRs) in the light chain are involved in the target interaction, only CDR3 within the heavy chain interacts with PD-1. Tislelizumab binds the front β-sheet of PD-1 in a very similar way as PD-L1 binds to PD-1, thereby blocking the PD-1/PD-L1 interaction with a higher affinity. A comparative analysis of PD-1 interactions with therapeutic antibodies targeting PD-1 provides a better understanding of the blockade mechanism of PD-1/PD-L1 interaction in addition to useful information for the improvement of therapeutic antibodies capable of diminishing checkpoint signaling for cancer immunotherapy.

PubMed: 32446372
DOI: 10.1016/j.bbrc.2020.04.121

実験手法

X-RAY DIFFRACTION (3.32 Å)