5GGS

PD-1 in complex with pembrolizumab Fab

5GGS の概要

• エントリーDOI: 10.2210/pdb5ggs/pdb
• 分子名称: heavy chain, light chain, Programmed cell death protein 1, ... (4 entities in total)
• 機能のキーワード: antibody, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Membrane; Single-pass type I membrane protein: Q15116
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 125778.10

構造登録者

Heo, Y.S. (登録日: 2016-06-16, 公開日: 2016-11-09, 最終更新日: 2016-11-16)

主引用文献

Lee, J.Y.,Lee, H.T.,Shin, W.,Chae, J.,Choi, J.,Kim, S.H.,Lim, H.,Won Heo, T.,Park, K.Y.,Lee, Y.J.,Ryu, S.E.,Son, J.Y.,Lee, J.U.,Heo, Y.S.
Structural basis of checkpoint blockade by monoclonal antibodies in cancer immunotherapy
Nat Commun, 7:13354-13354, 2016

PubMed Abstract: Cancer cells express tumour-specific antigens derived via genetic and epigenetic alterations, which may be targeted by T-cell-mediated immune responses. However, cancer cells can avoid immune surveillance by suppressing immunity through activation of specific inhibitory signalling pathways, referred to as immune checkpoints. In recent years, the blockade of checkpoint molecules such as PD-1, PD-L1 and CTLA-4, with monoclonal antibodies has enabled the development of breakthrough therapies in oncology, and four therapeutic antibodies targeting these checkpoint molecules have been approved by the FDA for the treatment of several types of cancer. Here, we report the crystal structures of checkpoint molecules in complex with the Fab fragments of therapeutic antibodies, including PD-1/pembrolizumab, PD-1/nivolumab, PD-L1/BMS-936559 and CTLA-4/tremelimumab. These complex structures elucidate the precise epitopes of the antibodies and the molecular mechanisms underlying checkpoint blockade, providing useful information for the improvement of monoclonal antibodies capable of attenuating checkpoint signalling for the treatment of cancer.

PubMed: 27796306
DOI: 10.1038/ncomms13354

実験手法

X-RAY DIFFRACTION (1.997 Å)