5JDR

Structure of PD-L1

5JDR の概要

• エントリーDOI: 10.2210/pdb5jdr/pdb
• 分子名称: Programmed cell death 1 ligand 1 (2 entities in total)
• 機能のキーワード: immunosuppression, immune system
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Isoform 1: Cell membrane ; Single-pass type I membrane protein . Isoform 2: Endomembrane system ; Single-pass type I membrane protein : Q9NZQ7
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 54339.58

構造登録者

Zhou, A.,Wei, H. (登録日: 2016-04-17, 公開日: 2017-04-12, 最終更新日: 2024-11-13)

主引用文献

Zhang, F.,Wei, H.,Wang, X.,Bai, Y.,Wang, P.,Wu, J.,Jiang, X.,Wang, Y.,Cai, H.,Xu, T.,Zhou, A.
Structural basis of a novel PD-L1 nanobody for immune checkpoint blockade.
Cell Discov, 3:17004-17004, 2017

PubMed Abstract: The use of antibodies to target immune checkpoints, particularly PD-1/PD-L1, has made a profound impact in the field of cancer immunotherapy. Here, we identified KN035, an anti-PD-L1 nanobody that can strongly induce T-cell responses and inhibit tumor growth. The crystal structures of KN035 complexed with PD-L1 and free PD-L1, solved here at 1.7 and 2.7 Å resolution, respectively, show that KN035 competes with PD-1 (programmed death protein 1) for the same flat surface on PD-L1, mainly through a single surface loop of 21 amino acids. This loop forms two short helices and develops key hydrophobic and ionic interactions with PD-L1 residues, such as Ile54, Tyr56 and Arg113, which are also involved in PD-1 binding. The detailed mutagenesis study identified the hotspot residues of the PD-L1 surface and provides an explanation for the stronger (~1 000-fold) binding of KN035 to PD-L1 than PD-1 and its lack of binding to PD-L2. Overall, this study reveals how a single immunoglobulin-variable scaffold of KN035 or PD-1 can bind to a flat protein surface through either a single surface loop or beta-sheet strands; and provides a basis for designing new immune checkpoint blockers and generating bi-specific antibodies for combination therapy.

PubMed: 28280600
DOI: 10.1038/celldisc.2017.4

実験手法

X-RAY DIFFRACTION (2.7 Å)