6sru

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

spinqualitylabelsall models 6sru, resolution 2.53Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.532Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed In the development of PD-L1-blocking therapeutics, it is essential to transfer initial in vitro findings into proper in vivo 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 (m) PD-L1 and analyze its similarity to the human (h) PD-L1. We show that mPD-L1 interacts with hPD-1 and provides a negative signal toward activated Jurkat T cells. We also show major differences in druggability between the hPD-L1 and mPD-L1 using therapeutic antibodies, a macrocyclic peptide, and small molecules. Our study indicates that while the amino acid sequence is well conserved between the hPD-L1 and mPD-L1 and overall structures are almost identical, crucial differences determine the interaction with anti-PD-L1 agents, that cannot be easily predicted in silico. Human and mouse PD-L1: similar molecular structure, but different druggability profiles.,Magiera-Mularz K, Kocik J, Musielak B, Plewka J, Sala D, Machula M, Grudnik P, Hajduk M, Czepiel M, Siedlar M, Holak TA, Skalniak L iScience. 2020 Dec 24;24(1):101960. doi: 10.1016/j.isci.2020.101960. eCollection , 2021 Jan 22. PMID:33437940 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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