6SRU

Structure of Ig-like V-type domian of mouse Programmed cell death 1 ligand 1 (PD-L1)

6SRU の概要

• エントリーDOI: 10.2210/pdb6sru/pdb
• 分子名称: Programmed cell death 1 ligand 1 (2 entities in total)
• 機能のキーワード: pd-l1, immune checkpoint protein, immune system
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 133352.18

構造登録者

Magiera-Mularz, K.,Sala, D.,Grudnik, P.,Holak, T.A. (登録日: 2019-09-06, 公開日: 2021-02-03, 最終更新日: 2024-10-23)

主引用文献

Magiera-Mularz, K.,Kocik, J.,Musielak, B.,Plewka, J.,Sala, D.,Machula, M.,Grudnik, P.,Hajduk, M.,Czepiel, M.,Siedlar, M.,Holak, T.A.,Skalniak, L.
Human and mouse PD-L1: similar molecular structure, but different druggability profiles.
Iscience, 24:101960-101960, 2021

PubMed Abstract: In the development of PD-L1-blocking therapeutics, it is essential to transfer initial findings into proper animal models. Classical immunocompetent mice are attractive due to high accessibility and low experimental costs. However, it is unknown whether inter-species differences in PD-L1 sequence and structure would allow for human-mouse cross applications. Here, we disclose the first structure of the mouse () PD-L1 and analyze its similarity to the human () PD-L1. We show that PD-L1 interacts with PD-1 and provides a negative signal toward activated Jurkat T cells. We also show major differences in druggability between the PD-L1 and PD-L1 using therapeutic antibodies, a macrocyclic peptide, and small molecules. Our study indicates that while the amino acid sequence is well conserved between the PD-L1 and PD-L1 and overall structures are almost identical, crucial differences determine the interaction with anti-PD-L1 agents, that cannot be easily predicted .

PubMed: 33437940
DOI: 10.1016/j.isci.2020.101960

実験手法

X-RAY DIFFRACTION (2.532 Å)