6SRU

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

Summary for 6SRU

• Entry DOI: 10.2210/pdb6sru/pdb
• Descriptor: Programmed cell death 1 ligand 1 (2 entities in total)
• Functional Keywords: pd-l1, immune checkpoint protein, immune system
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 10
• Total formula weight: 133352.18

Authors

Magiera-Mularz, K.,Sala, D.,Grudnik, P.,Holak, T.A. (deposition date: 2019-09-06, release date: 2021-02-03, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.532 Å)