5B8C

High resolution structure of the human PD-1 in complex with pembrolizumab Fv

5B8C の概要

• エントリーDOI: 10.2210/pdb5b8c/pdb
• 分子名称: Pembrolizumab light chain variable region (PemVL), Pembrolizumab heavy chain variable region (PemVH), 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; 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: 12
• 化学式量合計: 168002.49

構造登録者

Horita, S.,Shimamura, T.,Iwata, S.,Nomura, N. (登録日: 2016-06-14, 公開日: 2016-10-26, 最終更新日: 2024-11-20)

主引用文献

Horita, S.,Nomura, Y.,Sato, Y.,Shimamura, T.,Iwata, S.,Nomura, N.
High-resolution crystal structure of the therapeutic antibody pembrolizumab bound to the human PD-1
Sci Rep, 6:35297-35297, 2016

PubMed Abstract: Pembrolizumab is an FDA-approved therapeutic antibody that targets the programmed cell death-1 (PD-1) to block the immune checkpoint pathway for the treatment of various types of cancer. It receives remarkable attention due to the high degree of efficacy. Very recently, the crystal structure of the Fab fragment of pembrolizumab (PemFab) in complex with the extracellular domain of human PD-1 (PD-1) was reported at a resolution of 2.9 Å. However, this relatively low-resolution structural data fails to provide sufficient information on interfacial water molecules at the binding interface that substantially contribute to affinity and specificity between the therapeutic antibody and target. Here, we present the independently determined crystal structure of the Fv fragment of pembrolizumab (PemFv) in complex with the PD-1 at a resolution of 2.15 Å. This high-resolution structure allows the accurate mapping of the interaction including water-mediated hydrogen bonds and provides, for the first time, a coherent explanation of PD-1 antagonism by pembrolizumab. Our structural data also provides new insights into the rational design of improved anti-PD-1 therapeutics.

PubMed: 27734966
DOI: 10.1038/srep35297

実験手法

X-RAY DIFFRACTION (2.146 Å)